KR101286617B1 - Method for preparing ［1,2,3］-oxathiazolidine-2,2-dioxide or ［1,2,5］-thiadiazolidine-1,1-dioxide derivatives - Google Patents
Method for preparing ［1,2,3］-oxathiazolidine-2,2-dioxide or ［1,2,5］-thiadiazolidine-1,1-dioxide derivatives Download PDFInfo
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- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
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- C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
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Abstract
The present invention relates to a novel process for preparing [1,2,3] -oxathiazolidine-2,2-dioxide or [1,2,5] -thiadiazolidine-1,1-dioxide derivative. In the preparation method of the present invention, 5 H- [1,2,3] -oxathiazole-2,2-dioxide or [1,2,5] -thiadiazoline-1,1-dioxide is reacted with a rhodium compound catalyst and hydrogen. [1,2,3] -oxathiazolidine-2,2-dioxide or [1,2,5] -thiadiazolidine-1,1-dioxide with enantiomerically pure reactions by asymmetric reduction in the presence of a donor Derivatives can be prepared simply and efficiently.
Description
The present invention efficiently produces enantiomerically pure [1,2,3] -oxathiazolidine-2,2-dioxide or [1,2,5] -thiadiazolidine-1,1-dioxide derivative It relates to a novel manufacturing method that can be done.
Enantiomerically pure [1,2,3] -oxathiazolidine-2,2-dioxide and [1,2,5] -thiadiazolidine-1,1-dioxide derivatives are useful in organic synthesis. Due to high demand.
A process for preparing a conventional enantiomerically pure [1,2,3] -oxathiazolidine-2,2-dioxide, in 2,2,2-trifluoroethanol (TFE) solvent as in Scheme 1 below. 5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in Pd (CF 3 CO 2) 2 and (S, S) - f - a bar or a plate ((S, S) - f - binaphane) and hydrogenation under high hydrogen pressure of 600 psi is known (Org. Lett. 2008, 10, 2071).
[Reaction Scheme 1]
Wherein R is phenyl, 4-fluorophenyl, 4-methylphenyl, 3-methoxyphenyl, 2-methylphenyl.
However, the above method uses (S, S) -f-binaphan of the following structural formula as a ligand with a relatively high supported amount of catalyst and a high price.
In addition, it is carried out in a reaction solvent of very polar 2,2,2-trifluoroethanol, and the asymmetric hydrogenation reaction with high pressure hydrogen requires a high pressure reactor and uses a dangerous hydrogen gas. Difficult to apply to the production process.
5 H- [1,2,3] -oxathiazole-2,2-dioxide used as starting material in the preparation of the [1,2,3] -oxathiazolidine-2,2-dioxide is represented by the following reaction scheme: as shown in 2, a- hydroxy ketone (a-hydroxy ketone) and N -..-chloro-sulfonyl isocyanate is produced by a reaction process with the (N -chlorosulfonyl isocyanate) (Org Lett 2008, 10, 2071, and J Am. Chem. Soc. 2001, 123, 6935).
[Reaction Scheme 2]
Specifically, formic acid was added to N -chlorosulfonyl isocyanate at 0 ° C. to prepare ClSO 2 NH 2 in solution, which was added to a solution containing a-hydroxy ketone and pyridine at 0 ° C. and then overnight at 10 ° C. Stir. The resulting reaction was distilled under reduced pressure to produce a by-product a-chloroketone, an intermediate product sulfamate ester, and a target product, 5 H- [1,2,3] -oxathiazole-2,2-dioxide. To obtain a mixed product. To this, p-TsOH and high boiling point solvent are added to remove the water produced by heating, and the intermediate product sulfamate ester is 5 H- [1,2,3] -oxathiazole-2,2-dioxide as the target product. Is converted to and finally subjected to column chromatography to remove by-product a-chloro ketone to give 5 H- [1,2,3] -oxathiazole-2,2-dioxide.
However, the method uses N -chlorosulfonyl isocyanate, which is not easy to handle and is expensive, and there is a violent gas (CO 2 , CO) generation during the production of ClSO 2 NH 2 in solution phase, and the manufacturing process is complicated. there is a problem.
This makes it possible to efficiently and efficiently enantiomerically pure [1,2,3] -oxathiazolidine-2,2-dioxide or [1,2,5] -thiadiazolidine-1,1-dioxide derivative. There is a need for development of methods that can be manufactured.
Accordingly, it is an object of the present invention to provide enantiomerically pure [1,2,3] -oxathiazolidine-2,2-dioxide or [1,2,5] -thiadiazolidine-1,1-dioxide derivatives. It is to provide a method for efficiently manufacturing.
The present invention is also effective in the 5 H- [1,2,3] -oxathiazole-2,2-dioxide and [1,2,5] -thiadiazoline-1,1-dioxide used in the above production method. It provides a method of manufacturing.
In order to achieve the above object, the present invention provides a compound of formula 1a or 1b having an optical activity by asymmetric reduction of the compound of formula 2 in the presence of a rhodium compound catalyst containing a pentamethylcyclopentadienyl group and a hydrogen donor Provides a way to:
[Formula 1a]
[Chemical Formula 1b]
[Formula 2]
Where
R 1 and R 2 are each independently a hydrogen or alkyl group of C 1 -6,
X is O or NH,
Y is a phenyl group, naphthalene group, Pew group, a thienyl group, a benzo Pew group, is selected from benzothienyl group and a pyridinyl group consisting of groups, the Y is halo for halogen, C 1 -6 alkyl, C 1 -6 alkyl, an alkoxy group of C 1 -6, can be substituted with a substituent selected from aralkyl oxy group and a nitro group consisting of C 7 -24.
Preferably the rhodium compound catalyst is a compound having the structure of formula 3a or 3b:
[Chemical Formula 3]
(3b)
In the above formula
Ph is a phenyl group and Ts is a tosyl group.
The present invention also provides a process for preparing a compound of Formula 2 by reacting a-hydroxy ketone of Formula 4 with reflux with sulfamide of Formula 5 or under acidic conditions:
[Formula 4]
[Chemical Formula 5]
Where
R 1 and R 2 are each independently a hydrogen or alkyl group of C 1 -6,
R 3 and R 4 are each independently a group selected from an alkoxy group and a haloalkoxy group consisting of C 1 -6 of the alkyl group of C 1 -6 mono- or di-substituted amino group, a C 1 -6, wherein R 3 And at least one of R 4 is a primary amino group,
Y is as defined above.
According to the preparation method of the present invention, enantiomerically pure [1,2,3] -oxathiazolidine-2,2-dioxide or [1,2,5] -thiadiazolidine-1,1-dioxide derivative Can be produced simply and efficiently.
Hereinafter, the present invention will be described in more detail.
As used herein, "C 1-6 alkyl" refers to a linear or branched saturated C 1 to C 6 hydrocarbon radical chain. Specific examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl and hexyl.
As used herein, "C 1-6 alkoxy" refers to the group -OR a , wherein R a is C 1-6 alkyl as defined above. Specific examples include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, t-butoxy, and the like.
As used herein, "C 1-6 haloalkyl" refers to a C 1-6 alkyl group substituted with one or more halogens, wherein C 1-6 alkyl is as defined above. Specific examples include, but are not limited to, trifluoromethyl, trichloroethyl, and the like.
As used herein, the term “C 6-18 aryl” refers to an aryl group having 6 to 18 carbon atoms, as well as fused groups such as naphthyl, phenanthrenyl, and the like, as well as monocyclic or bicyclic such as phenyl, substituted phenyl, and the like. And click aromatic rings. Specific examples include, but are not limited to, phenyl, toluyl, xylyl, biphenyl, naphthyl, and the like.
As used herein, “C 7-24 aralkyloxy” means (C 7-24 aralkyl) -O—, wherein C 7-24 aralkyl is C 1-6 substituted with a C 6-18 aryl group An alkyl group, wherein the aryl group and alkyl group are as defined above. Specific examples include, but are not limited to, benzyloxy, phenethyloxy, phenylpropyloxy, and the like.
The process for preparing the compound of formula 1a or 1b according to the present invention is characterized by the use of a process by catalytic asymmetric transfer hydrogenation.
Specifically, as shown in Scheme 3, a compound of formula 1a or 1b having an optical activity by asymmetrically reducing the compound of formula 2 in the presence of a rhodium compound catalyst containing a pentamethylcyclopentadienyl group and a hydrogen donor Manufactures:
Scheme 3
Where
R 1 and R 2 each independently represents a hydrogen or a C 1 -6, preferably a hydrogen or a methyl group,
X is O or NH,
Y is a phenyl group, naphthalene group, Pew group, a thienyl group, a benzo Pew group, is selected from benzothienyl group and a pyridinyl group consisting of groups, the Y is halo for halogen, C 1 -6 alkyl, C 1 -6 alkyl, an alkoxy group of C 1 -6, can be substituted with a substituent selected from aralkyl oxy group and a nitro group consisting of C 7 -24.
Preferably, Y is phenyl, 2-furyl, 2-thienyl, 3-furyl, 3-thienyl, 2-benzofuryl, 2-benzothienyl, 3-benzofuryl, 3-benzothienyl, 2 -Selected from the group consisting of pyridinyl, 3-pyridinyl and 4-pyridinyl, the group consisting of methyl, ethyl, methoxy, ethoxy, benzyloxy, fluoro, chloro, bromo, trifluoromethyl and nitro groups It may be substituted with one or more substituents selected from.
Rhodium compound catalysts having a pentamethylcyclopentadienyl group (generally represented as C 5 Me 5 , Cp *) used in the present invention are known materials and can be prepared by conventional methods. Specific examples thereof include (pentamethylcyclopentadienyl) rhodium (III) chloride dimer [Rh (C 5 Me 5 ) Cl 2 ] 2 in methylene chloride solvent, 1,2-diphenylethylene-N- () having optical activity. It is known that the reaction obtained by adding p -toluenesulfonyl) diamine (TsDPEN) and triethylamine is washed with water and then recrystallized to give a yield of 70% (Mashima et al., Chem . Letters, 1199 (1998). ) And Chem . Letters , 1201 (1998).
In the present invention, 1,2-diphenylethylene-N having an optical activity with pentamethylcyclopentadienyl) rhodium (III) chloride dimer [Rh (C 5 Me 5 ) Cl 2 ] 2 in a nonpolar solvent such as methylene chloride. The rhodium compound catalyst can be prepared quantitatively by reacting with-( p -toluenesulfonyl) diamine (TsDPEN) and optionally triethylamine and then removing the solvent from the resulting reactant.
The optically active 1,2-diphenylethylene-N- ( p -toluenesulfonyl) diamine is preferably used in 2 equivalents to 1 equivalent of (pentamethylcyclopentadienyl) rhodium (III) chloride dimer, When triethylamine is used, triethylamine is preferably used in 4 equivalents with respect to 1 equivalent of (pentamethylcyclopentadienyl) rhodium (III) chloride dimer.
The method for preparing the rhodium compound catalyst according to the present invention is not only easier to prepare the catalyst than the conventional method, but also excellent in the synthesis yield of the catalyst, and in terms of efficiency, the catalyst equivalent to that prepared by the conventional methods. Ability.
The rhodium compound catalyst prepared by the above method is simply represented by TsDPEN-RhCl-Cp *, and in the present invention, a structure of (R, R) -TsDPEN-RhCl-Cp * having the structure of Formula 3a or having the structure of Formula 3b (S, S) -TsDPEN-RhCl-Cp * can be used.
[Chemical Formula 3]
(3b)
Wherein Ph is a phenyl group and Ts is a tosyl group.
The rhodium compound catalyst is a molar ratio of the substrate to the rhodium compound catalyst (the number of moles of the substrate / the number of moles of the catalyst), and is used in an amount of 100 to 10,000 moles of the formula (2) per 1 mole of the rhodium compound catalyst. It is preferable.
The hydrogen donor may be used as a material for donating hydrogen according to thermal or catalysis, and formic acid, a metal salt of formic acid, an ammonium salt of formic acid, and a mixture of formic acid and an amine (eg, Et 3 N) may be used.
The hydrogen donor can be used on its own or in solution without the use of a solvent. When used in the solution phase, the solvent may be ethyl acetate, toluene, methylene chloride, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), acetonitrile, isopropanol and the like.
The compound of formula 2 used as a starting material in the preparation of the compound of formula 1a or 1b may also be prepared by a conventional method with a known material, and in the present invention, the compound of formula 2 may be a-hydroxy ketone sulfamide It can be prepared by heating and refluxing in a reaction solvent with or reacting with sulfamide in a reaction solvent under acidic conditions.
Accordingly, the present invention provides a novel method for preparing the compound of Formula 2.
That is, the method for preparing the compound of Formula 2 according to another embodiment of the present invention is heated to reflux in the reaction solvent and the sulfamide of the formula (5) in the reaction solvent, or in acidic conditions Reacting with sulfamides of Formula 5:
[Formula 4]
[Chemical Formula 5]
Where
R 1 and R 2 each independently represents a hydrogen or a C 1 -6, preferably a hydrogen or a methyl group,
R 3 and R 4 are each independently a group selected from an alkoxy group and a haloalkoxy group consisting of C 1 -6 of the alkyl group of C 1 -6 mono- or di-substituted amino group, a C 1 -6, wherein R 3 And at least one of R 4 is a primary amino group,
Y is as defined above.
Specifically, in the case of 5 H- [1,2,3] -oxathiazole-2,2-dioxide in which X is O in Formula 2, α-hydroxy ketone of Formula 4 is combined with sulfamide of Formula 5 It can be prepared by heating to reflux in the reaction solvent to remove ammonia / amine and water.
At this time, the reaction is preferably carried out in neutral conditions.
Α-hydroxy ketone of Formula 4 may be obtained by α-hydroxylation (α-hydroxylation) from a methyl ketone compound by a known method (Tetrahedron Letters, 1992, 33, 6065; J. Chem. PERKIN TRANS. 1989, 1781; Synthesis, 1985, 943; and Chem. Commun. 2001, 956). Specific examples of a-hydroxy ketones include 1-phenyl-2-hydroxyethanone, 1- (2-furyl) -2-hydroxyethanone, and 1- (2-thienyl) -2-hydroxyethanone , 1- (3-furyl) -2-hydroxyethanone, 1- (3-thienyl) -2-hydroxyethanone, 1- (2-benzofuryl) -2-hydroxyethanone, 1- (2-benzothienyl) -2-hydroxyethanone, 1- (3-benzofuryl) -2-hydroxyethanone, 1- (3-benzothienyl) -2-hydroxyethanone, 1- (2-pyridinyl) -2-hydroxyethanone, 1- (3-pyridinyl) -2-hydroxyethanone, 1- (4-pyridinyl) -2-hydroxyethanone or mixtures thereof and the like Can be mentioned.
The sulfamide of Formula 5 may include sulfamide compounds such as sulfamide, N, N' -dimethyl sulfamide, N, N' -diethyl sulfamide, etc .; Sulfamate ester compounds such as methyl sulfamate, ethyl sulfamate and 2,2,2-trichloroethyl sulfamate; Or mixtures thereof. At this time, in the case of using sulfamate ester, 5 H- [1,2,3] -oxathiazole-2,2-dioxide is prepared while removing alcohol and water.
As the reaction solvent usable in the reaction, benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dichlorobenzene, or a mixture thereof may be used.
In addition, in the case of [1,2,5] -thiadiazolin-1,1-dioxide in which X is NH in the formula (2), the α-hydroxy ketone of the formula (4) is sulfide of the formula (5) in a reaction solvent under acidic conditions. By reacting with 2 equivalents of water, the desired product can be prepared, [1,2,5] -thiadiazoline-1,1-dioxide.
The acidic conditions may be formed using inorganic acids such as hydrochloric acid, hydrochloric anhydride (HCl gas), sulfuric acid, sulfuric anhydride, nitric acid, organic acids such as trifluoroacetic acid, trifluoromethanesulfonic acid, or mixtures thereof. Preferably hydrochloric anhydride can be used.
As the reaction solvent, alcohol solvents such as methanol, ethanol, propanol, isopropanol, butanol and t-butanol may be used.
In the same manner as described above, enantiomerically from 5 H- [1,2,3] -oxathiazole-2,2-dioxide and [1,2,5] -thiadiazolin-1,1-dioxide derivative [1,2,3] -oxathiazolidine-2,2-dioxide of formula 1a which is pure cyclic sulfamidate and [cyclic sulfamide] of [1,2, 5] -thiadiazolidine-1,1-dioxide derivatives can be prepared:
[Formula 1a]
[Chemical Formula 1b]
In addition, the compounds of Formula 1a and 1b prepared by the production method of the present invention can be purified by conventional extraction, distillation, recrystallization, column chromatography, etc., the purity (ee) of the resulting compound (Daicel) This can be determined by HPLC using a column equipped with Chiralcel ® OD-H, AD-H, or OJ-H.
The production process according to the invention is not only easier and more economical to produce starting materials than any conventional method, but also the product can be obtained with a higher purity (ee) than any conventional asymmetric transfer hydrogenation process.
In addition, the [1,2,3] -oxathiazolidine-2,2-dioxide derivative, ie, a cyclic sulfamidate derivative, may be prepared by conventional methods, for example, enantiomerically pure agricultural, pharmaceutical intermediates, and fine chemicals. Or an aminoalcohol, diamine or amino acid used as a building block (Org. Lett. 2008, 10, 2071; J. Am. Chem. Soc. 2001, 123). , 6935; and Tetrahedron Letters, 2003, 59, 2581).
Hereinafter, the present invention will be described in more detail with reference to the following Examples and Comparative Examples. However, the following examples are only for illustrating the present invention, but the scope of the present invention is not limited or limited to these.
< Manufacturing example 1-1> [S, S]- TsDPEN - RhCl - Cp * / HClEt 3 N Preparation of the catalyst
0.10 g (0.16 mmol) of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer and ( 1S, 2S )-(-)-N- p in a 5 ml two-necked round bottom flask under an argon balloon 0.12 g (0.32 mmol) of tosyl 1,2-diphenylethylenediamine was added thereto, and 5 ml of anhydrous methylene chloride and 90 µl (0.65 mmol) of anhydrous triethyleneamine were added thereto, and the mixture was stirred at room temperature for 2 hours. The resulting reaction mixture was distilled off under reduced pressure, the solvent was evaporated and removed, and then dried under high vacuum for 2 hours to give 190 mg of the title compound as an orange powder. The catalyst was used several times in small amounts while kept under argon atmosphere.
Preparation Example 1-2 [R, R] -TsDPEN-RhCl-Cp * / HClEt 3 Preparation of N Catalyst
12.5 mg (0.02 mmol) of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer and ( 1R, 2R )-(-)-N- p in a 5 ml two-necked round bottom flask under an argon balloon After adding 14.6 mg (0.04 mmol) of -tosyl-1,2-diphenylethylenediamine, 2 ml of anhydrous methylene chloride and 11.5 µl (0.08 mmol) of anhydrous triethyleneamine were added, followed by stirring at room temperature for 2 hours. The resulting reaction mixture was distilled off under reduced pressure, the solvent was evaporated and removed, and then dried under high vacuum for 2 hours to give 35 mg of the title compound as an orange powder. The catalyst was used several times in small amounts while kept under argon atmosphere.
Preparation Example 1-3 Preparation of [R, R] -TsDPEN-RhCl-Cp * Catalysts
6.3 mg (0.01 mmol) of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer and ( 1R, 2R )-(-)-N- p in a 25 ml two-neck round bottom flask under an argon balloon After adding 7.3 mg (0.02 mmol) of tosyl 1,2-diphenylethylenediamine, 1 ml of anhydrous methylene chloride was added, followed by stirring at room temperature for 2 hours. The resulting reaction mixture was distilled off under reduced pressure to evaporate and remove the solvent, and dried under high vacuum for 4 hours to give 12 mg of the title compound as an orange powder. The catalyst was used several times in small amounts while kept under argon atmosphere.
Preparation Example 1-4 Preparation of [S, S] -TsDPEN-RhCl-Cp * Catalysts
In a 25 mL two-necked round bottom flask, 12.3 mg (0.02 mmol) of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer and ( 1S, 2S )-(-)-N- p under an argon balloon After adding 14.6 mg (0.04 mmol) of tosyl 1,2-diphenylethylenediamine, 1 ml of anhydrous methylene chloride was added, followed by stirring at room temperature for 2 hours. The resulting reaction mixture was distilled off under reduced pressure to evaporate and remove the solvent, and dried under high vacuum for 4 hours to give 12 mg of the title compound in the form of an orange powder. The catalyst was used several times in small amounts while kept under argon atmosphere.
Production Example 2-1 4-phenyl-5 H -[1,2,3] -oxathiazole-2,2-dioxide
2-hydroxyacetophenone (100 mg, 0.72 mmol) and sulfamide (105.5 mg, 1.1 mmol) are placed in a two-necked round bottom flask set with a condenser and dean-strak trap and xyl Dissolved with 10 mL of len. The mixed solution was refluxed at 180 ° C. and confirmed by thin layer chromatography (TLC), and reacted for about 3 hours until all of the 2-hydroxyacetophenone spots disappeared. The solvent of the reaction solution was distilled off under reduced pressure, and then extracted with ethyl acetate (EtOAc). The obtained organic layer was washed with distilled water and brine, dried over Na 2 SO 4 and filtered. The solvent in the filtrate was removed by distillation under reduced pressure, and the residue was separated and purified by flash silica column chromatography (hexane (Hex): ethyl acetate (EtOAc) = 2: 1) to obtain 87 mg of the title compound.
Yield: 61%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.92 (d, J = 8.5 Hz, 2H), 7.75 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.9 Hz, 2H), 5.58 (s , 2H);
13 C NMR (75 MHz, CDCl 3 ): δ 175.4, 135.9, 129.7, 128.9, 127.2, 74.4;
EIMS (70 eV) m / z (rel intensity) 197 (M +, 48), 103 (100).
< Manufacturing example 2-2> 4- (2- Methoxyphenyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-1 except for using 2-hydroxy-1- (2-methoxyphenyl) ethanone (0.72 mmol) instead of 2-hydroxyacetophenone. Was prepared.
Molecular weight: 227;
Yield: 66%;
1 H NMR (300 MHz, CDCl 3 ): δ 8.30 (dd, J = 7.9 and 1.7 Hz, 1H), 7.70-7.65 (m, 1H), 7.17-7.12 (m, 1H), 7.04 (d, J = 8.1 Hz, 1H), 5.59 (s, 2H), 3.98 (s, 3H);
EIMS (70 eV) m / z (rel intensity) 227 (M +, 5), 133 (100), 104 (60), 90 (24), 64 (32).
< Manufacturing example 2-3> 4- (3- Methoxyphenyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-1 except for using 2-hydroxy-1- (3-methoxyphenyl) ethanone (0.72 mmol) instead of 2-hydroxyacetophenone. Was prepared.
Molecular weight: 227;
Yield: 67%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.50 (t, J = 2.5 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.39-7.35 (m, 1H), 7.28-7.24 (m, 1H), 5.57 (s, 2H), 3.89 (s, 3H);
EIMS (70 eV) m / z (rel intensity) 227 (M +, 23), 133 (100), 103 (26), 90 (11).
< Manufacturing example 2-4> 4- (4- Methoxyphenyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-1 except for using 2-hydroxy-1- (4-methoxyphenyl) ethanone (0.72 mmol) instead of 2-hydroxyacetophenone. Was prepared.
Molecular weight: 227;
Yield: 69%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.87 (d, J = 9.1 Hz, 2H), 7.45 (d, J = 9.0 Hz, 2H), 5.54 (s, 2H), 3.93 (s, 3H);
EIMS (70 eV) m / z (rel intensity) 227 (M +, 19), 133 (100), 103 (21), 90 (18).
< Manufacturing example 2-5> 4- (3- Chlorophenyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-1, except for using 2-hydroxy-1- (3-chlorophenyl) ethanone (0.72 mmol) instead of 2-hydroxyacetophenone. Prepared.
Molecular weight: 232;
Yield: 60%;
1 H NMR (300 MHz, CDCl 3 ) δ 7.92 (t, J = 1.9 Hz, 1H), 7.81-7.77 (m, 1H), 7.73-7.69 (m, 1H), 7.49 (t, J = 7.9 Hz, 1H ), 5.57 (s, 2 H);
EIMS (70 eV) m / z (relintensity) 231 (M +, 19), 137 (100), 102 (13).
< Manufacturing example 2-6> 4- (4- Chlorophenyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-1, except that 2-hydroxy-1- (4-chlorophenyl) ethanone (0.72 mmol) was used instead of 2-hydroxyacetophenone. Prepared.
Molecular weight: 232;
Yield: 56%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.85 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H), 5.56 (s, 2H);
13 C NMR (75 MHz, CDCl 3 ): δ 177.7, 140.6, 131.1, 129.6, 126.0, 76.9;
EIMS (70 eV) m / z (relintensity) 231 (M +, 12), 136 (100), 102 (20), 75 (14).
< Manufacturing example 2-7> 4- (4- Trifluoromethylphenyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The procedure was carried out in the same manner as in Preparation Example 2-1, except that 2-hydroxy-1- (4-trifluoromethylphenyl) ethanone (0.72 mmol) was used instead of 2-hydroxyacetophenone. The compound was prepared.
Molecular weight: 265;
Yield: 65%;
1 H NMR (300 MHz, CDCl 3 ) δ 8.05 (d, J = 8.2 Hz, 2H), 7.83 (d, J = 8.2 Hz, 2H), 5.62 (s, 2H);
EIMS (70 eV) m / z (rel intensity) 265 (M +, 6), 171 (100), 152 (24), 144 (12), 121 (38).
< Manufacturing example 2-8> 4- (2- Naphthyl ) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-1, except for using 2-hydroxy-1- (2-naphthyl) ethanone (0.72 mmol) instead of 2-hydroxyacetophenone. Prepared.
Molecular weight: 247;
Yield: 57%;
1 H NMR (300 MHz, CDCl 3 ): δ 8.33 (s, 1H), 8.01 (d, J = 1.3 Hz, 2H), 7.95 (t, J = 9.4 Hz, 2H), 7.74-7.61 (m, 2H) , 5.73 (s, 2 H);
EIMS (70 eV) m / z (rel intensity) 247 (M +, 18), 153 (100), 126 (17).
< Manufacturing example 2-9> 4- Phenyl -5,5-dimethyl- [1,2,3] -oxathiazole-2,2- Dioxide
2-hydroxy-2-methyl propiophenone (500 mg, 3.04 mmol) and 2,2,2-trichloroethyl sulfamate (1.39 g, 7.69 mmol) set as condenser and Dean stock trap Placed in the bottom flask and dissolved in 30 mL of xylene. The mixed solution was refluxed at 180 ° C. for 27 hours by TLC until all of the 2-hydroxy-2-methyl propiophenone spots disappeared. The reaction solution was evaporated under reduced pressure, and extracted with ethyl acetate (EtOAc). The obtained organic layer was washed with distilled water and brine, dried over Na 2 SO 4 and filtered. The solvent in the filtrate was removed by evaporation and the residue was separated and purified by flash silica column chromatography (Hex: EtOA c = 2: 1) to give 527 mg of the title compound.
Yield: 77%;
1 H NMR (300 MHz, CDCl 3 ): δ 8.04 (d, J = 4.5 Hz, 2H), 7.68 (t, J = 7.5 Hz, 1H), 7.57 (t, J = 7.5 Hz, 2H), 1.95 (s , 6H);
13 C NMR (75 MHz, CDCl 3 ): δ 181.5, 134.9, 130.4, 129.4, 126.7, 95.3, 26.8;
EIMS (70 eV) m / z (rel intensity) 225 (M +, 2), 146 (16), 103 (100), 76 (34), 58 (98).
< Manufacturing example 2-10> 4- ( Furan -2-yl) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
Except for using 2-hydroxy-1- (furan-2-yl) ethanone (3.04 mmol) and toluene (30 mL) instead of 2-hydroxy-2-methyl propiophenone and xylene The title compound was prepared in the same manner as in Preparation Example 2-9.
Yield: 60%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.83-7.82 (m, 1H), 7.57 (dd, 1H, J = 3.7 and 0.6 Hz), 6.77 (dd, 1H, J = 3.7 and 1.7 Hz), 5.49 ( s, 2H);
13 C NMR (75 MHz, CDCl 3 ): δ 164.5, 150.1, 144.0, 122.0, 114,3, 73.5.
< Manufacturing example 2-11> 4- (thiophen-2-yl) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
Preparation Example 2 except for using 2-hydroxy-1- (thiophen-2-yl) ethanone (3.04 mmol) instead of 2-hydroxy-1- (furan-2-yl) ethanone The title compound was prepared in the same manner as in the method of -10.
Yield: 46%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.94 (d, 1H, J = 5.0 Hz), 7.75 (d, 1H, J = 3.9 Hz), 7.29 (t, 1H, J = 4.4 Hz), 5.53 (s , 2H).
< Manufacturing example 2-12> 4- ( Benzofuran -2-yl) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
Preparation Example 2, except that 2-hydroxy-1- (benzofuran-2-yl) ethanone (3.04 mmol) was used instead of 2-hydroxy-1- (furan-2-yl) ethanone. The title compound was prepared in the same manner as in the method of -10.
Yield: 52%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.25 (s, 1H), 7.94 (d, 1H, J = 7.9 Hz), 7.84 (d, 1H, J = 7.9 Hz), 7.66 (t, 1H, J = 7.6 Hz), 7.46 (t, 1H, J = 7.7 Hz), 6.07 (s, 2H);
13 C NMR (75 MHz, DMSO-d 6 ): δ 168.0, 156.2, 144.1, 130.0, 126.7, 124.8, 123.9, 120.0, 112.4, 75.9.
< Manufacturing example 2-13> 4- ( Benzothiophene -3-yl) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
The above preparation except that 2-hydroxy-1- (benzothiophen-3-yl) ethanone (3.04 mmol) was used instead of 2-hydroxy-1- (furan-2-yl) ethanone. The title compound was prepared in the same manner as in 2-10.
Yield: 42%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 9.09 (s, 1H), 8.62 (d, 1H, J = 8.1 Hz), 8.23 (d, 1H, J = 8.1 Hz), 7.68-7.56 (m, 2H), 6.16 (s, 2H);
13 C NMR (75 MHz, DMSO-d 6 ): 171.7, 144.2, 139.4, 135.0, 126.6, 126.2, 124.1, 123.7, 123.6, 76.8.
< Manufacturing example 2-14> 4- (pyridin-3-yl) -5H- [1,2,3] -oxathiazole-2,2- Dioxide
Preparation Example 2- except that 2-hydroxy-1- (pyridin-3-yl) ethanone (3.04 mmol) was used instead of 2-hydroxy-1- (furan-2-yl) ethanone. The title compound was prepared in the same manner as in 10.
Yield: 25%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 9.14 (d, 1H, J = 1.5 Hz), 8.93 (dd, 1H, J = 5.0 and 1.5 Hz), 8.41 (dt, 1H, J = 7.7 and 1.8 Hz), 7.70 (ddd, 1H, J = 8.1, 4.9 and 0.7 Hz), 6.17 (s, 2H);
EIMS (70 eV) m / z (rel intensity) 198 (M +, 22), 104 (100), 77 (27).
< Manufacturing example 2-15> 3- Phenyl -1,2,5- Thiadiazoline -1,1- Dioxide
500 mg (3.67 mmol) of 2-hydroxyacetophenone and 529 mg (5.51 mmol) of sulfamide were placed in a two-necked round bottom flask and dissolved in 20 mL of ethanol. 5.87 mL (7.34 mmol) of 1.25 M HCl methanol solution (methanolic HCl) was added to the prepared solution, and the reaction was confirmed by TLC while refluxing at 110 ° C. for 24 hours until all of the 2-hydroxyacetophenone spots disappeared. The reaction solution was distilled under reduced pressure, and extracted with ethyl acetate (EtOAc). The obtained organic layer was washed with distilled water and brine, dried over Na 2 SO 4 and filtered. The solvent in the filtrate was removed by evaporation and the residue was separated and purified by flash silica column chromatography (Hex: EtOAc = 2: 1) to give 608 mg of the title compound.
Yield: 84%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.01 (d, J = 4.8 Hz, 2H), 7.93 (t, J = 2.7 Hz, 1H), 7.73 (t, J = 4.5 Hz, 1H), 7.60 (t, J = 4.8 Hz, 2H), 4.87 (d, J = 3.0 Hz, 2H);
13 C NMR (75 MHz, DMSO-d 6 ): 177.4, 134.5, 129.3, 129.0, 128.9, 52.6;
EIMS (70 eV) m / z (rel intensity) 196 (M +, 35), 132 (39), 105 (82), 77 (100).
< Manufacturing example 2-16> 3- (2- Methoxyphenyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except that 2-hydroxy-1- (2-methoxyphenyl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. Was prepared.
Molecular Weight: 226
Yield: 25%
1 H NMR (300 MHz, CDCl 3 ): δ 8.25 (dd, J = 8.0 and 1.9 Hz, 1H), 7.60 (t, J = 8.3 Hz, 1H), 7.10-7.00 (m, 2H), 4.82 (br, 1H), 4.81 (s, 2H), 3.94 (s, 3H);
EIMS (70 eV) m / z (rel intensity) 226 (M +, 5), 133 (100), 104 (56), 90 (17).
< Manufacturing example 2-17> 3- (3- Methoxyphenyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except for using 2-hydroxy-1- (3-methoxyphenyl) ethanone (3.67 mmol) instead of 2-hydroxyacetophenone. Was prepared.
Molecular weight: 226.2523;
Yield: 41%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 7.94 (s, 1H), 7.60-7.57 (m, 1H), 7.53-7.47 (m, 2H), 7.31-7.27 (m, 1H), 4.84 (d , 2H, J = 2.9 Hz), 3.83 (s, 1H);
13 C NMR (75 MHz, DMSO-d 6 ): 177.6, 159.9, 130.83 m 130.6, 121.7, 121.0, 113.61, 55.8, 53.1;
EIMS (70 eV) m / z (relintensity) 226 (M +, 17), 133 (100), 103 (30), 90 (13);
HRMS: Calcd for C 9 H 10 N 2 0 3 S (M < + >): 226.0412, found: 226.0407.
< Manufacturing example 2-18> 3- (4- Methoxyphenyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except for using 2-hydroxy-1- (4-methoxyphenyl) ethanone (3.67 mmol) instead of 2-hydroxyacetophenone. Was prepared.
Molecular weight: 226;
Yield: 30%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 7.98 (d, J = 9.0 Hz, 2H), 7.79 (t, J = 5.2 Hz, 1H), 7.14 (d, J = 9.0 Hz, 2H), 4.81 (d, J = 5.0 Hz, 2H), 3.88 (s, 3H);
EIMS (70 eV) m / z (rel intensity) 226 (M +, 7), 133 (100), 103 (22), 90 (22), 63 (11).
< Manufacturing example 2-19> 3- (3- Chlorophenyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except that 2-hydroxy-1- (3-chlorophenyl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. Prepared.
Molecular weight: 231;
Yield: 43%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.92 (t, J = 1.9 Hz, 1H), 7.82-7.79 (m, 1H), 7.67-7.63 (m, 1H), 7.49 (t, J = 8.1 Hz, 1H), 4.84-4.76 (m, 1H), 4.74 (d, J = 5.4 Hz, 2H);
EIMS (70 eV) m / z (rel intensity) 230 (M +, 4), 128 (100), 101 (31), 75 (14).
< Manufacturing example 2-20> 3- (4- Chlorophenyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Production Example 2-15, except that 2-hydroxy-1- (4-chlorophenyl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. Prepared.
Molecular weight: 230.6714;
Yield: 53%,
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.01 (d, 2H, J = 8.5 Hz), 7.99-7.92 (m, 1H), 7.66 (d, 2H, J = 8.5 Hz), 4.84 (d, 2H, J = 4.9 Hz);
13 C NMR (75 MHz, DMSO-d 6 ): 176.8, 139.8, 131.1, 129.7, 128.3, 53.0; EIMS (70 eV) m / z (relintensity) 230 (M +, 7), 137 (100), 102 (24), 75 (16);
HRMS: Calcd for C 8 H 7 ClN 2 0 2 S (M < + >): 229.9917, found: 229.9909.
< Manufacturing example 2-21> 3- (4- Trifluoromethylphenyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except that 2-hydroxy-1- (4-trifluoromethylphenyl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. Was prepared.
Molecular weight: 264;
Yield: 42%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.23 (d, J = 9.0 Hz, 2H), 8.12 (t, J = 4.5 Hz, 1H), 7.99 (d, J = 9.0 Hz, 2H), 4.94 (d, J = 4.7 Hz, 2H);
EIMS (70 eV) m / z (rel intensity): 265 (M +, 1), 172 (100), 152 (24), 144 (15), 121 (34).
< Manufacturing example 2-22> 3- (2- Naphthyl ) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Production Example 2-15, except that 2-hydroxy-1- (2-naphthyl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. Prepared.
Molecular weight: 246;
Yield: 66%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.71 (s, 1H), 8.15-8.05 (m, 4H), 7.77-7.65 (m, 2H), 7.31 (br, 1H), 5.02 (s, 2H );
EIMS (70 eV) m / z (rel intensity) 246 (M +, 11), 153 (100), 125 (20).
< Manufacturing example 2-23> 3- ( Furan -2-yl) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except for using 2-hydroxy-1- (furan-2-yl) ethanone (3.67 mmol) instead of 2-hydroxyacetophenone. Was prepared.
Yield: 12%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.22 (dd, 1H, J = 1,7 and 0.7 Hz), 7.76 (t, 1H, J = 5.2 Hz), 7.69 (dd, 1H, J = 3.7 And 0.7 Hz), 6.88 (dd, 1H, J = 3.7 and 1.7 Hz), 4.68 (d, 2H, J = 5.4 Hz).
< Manufacturing example 2-24> 3- (thiophen-2-yl) -1,2,5- Thiadiazoline -1,1- Dioxide
The procedure was carried out in the same manner as in Preparation Example 2-15, except that 2-hydroxy-1- (thiophen-2-yl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. The compound was prepared.
Yield: 27%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.20 (dd, 1H, J = 5.1 and 1.2 Hz), 8.05 (dd, 1H, J = 3.9 and 1.1 Hz), 7.85 (t, 1H, J = 5.4 Hz), 7.36 (dd, 1H, J = 5.0 and 3.9 Hz), 4.82 (d, 2H, J = 5.4 Hz).
< Manufacturing example 2-25> 3- ( Benzofuran -2-yl) -1,2,5- Thiadiazoline -1,1- Dioxide
The procedure was carried out in the same manner as in Preparation Example 2-15, except that 2-hydroxy-1- (benzofuran-2-yl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. The compound was prepared.
Yield: 21%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.13 (s, 1H), 7.96 (t, 1H, J = 4.8 Hz), 7.89 (d, 1H, J = 7.9 Hz), 7.80 (d, 1H, J = 8.3 Hz), 7.61 (td, 1H, J = 7.1 and 1.2 Hz), 7.43 (t, 1H, J = 7.9 Hz), 4.83 (d, 2H, J = 4.9 Hz);
13 C NMR (75 MHz, DMSO-d 6 ): 167.8, 156.4, 146.5, 129.7, 127.3, 124.9, 124.0, 118.1, 112.7, 52.5.
< Manufacturing example 2-26> 3- ( Benzothiophene -3-yl) -1,2,5- Thiadiazoline -1,1- Dioxide
The same procedure as in Preparation Example 2-15 was carried out except that 2-hydroxy-1- (benzothiophen-3-yl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. The title compound was prepared.
Yield: 66%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 9.04 (s, 1H), 8.67 (d, 1H, J = 7.9 Hz), 8.19 (d, 1H, J = 7.9 Hz), 7.81 (t, 1H, J = 4.9 Hz), 7.64-7.52 (m, 2H), 4.92 (d, 2H, J = 5.3 Hz);
13 C NMR (75 MHz, DMSO-d 6 ): 171.4, 141.7, 139.5, 135.4, 126.3, 126.0, 125.8, 124.5, 123.4, 53.4.
< Manufacturing example 2-27> 3- (pyridin-3-yl) -1,2,5- Thiadiazoline -1,1- Dioxide
The title compound was prepared in the same manner as in Preparation Example 2-15, except that 2-hydroxy-1- (pyridin-3-yl) ethanone (3.67 mmol) was used instead of 2-hydroxyacetophenone. Was prepared.
Yield: 18%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 9.13 (d, 1H, J = 2.1 Hz), 8.85 (dd, 1H, J = 4.8 and 1.6 Hz), 8.37 (dt, 1H, J = 8.1 and 1.9 Hz), 8.04 (t, 1H, J = 4.7 Hz), 7.6 (dd, 1H, J = 8.0 and 4.8 Hz), 4.9 (d, 2H, J = 4.8 Hz);
13 C NMR (75 MHz, DMSO-d 6 ): 176.2, 154.6, 149.7, 136.4, 125.3, 124.2, 52.7.
< Example 1> (R) -4- Phenyl -[1,2,3]- Oxathiazolidine -2,2- Dioxide
The 4-phenyl -5 H produced in Production Example 2-1 - [l, 2,3] oxazole prepared from thiazole-2,2-dioxide (197 mg, 1 mmol) and Preparation Example 1-1 [ S, S] -TsDPEN-RhCl-Cp * / Et 3 NHCl (3.88 mg, 0.005 equiv) was dissolved completely in ethyl acetate, and then mixed with HCO 2 H and Et 3 N (molar ratio = 5: 2) 0.2 mL was added and reacted at room temperature under a nitrogen atmosphere. The reaction is confirmed by a TLC 4- phenyl -5 H - it was carried out for about an hour until it disappears all of the oxa-thiazole-2,2-dioxide spot - [l, 2,3]. The resulting reaction solution was diluted with EtOAc and washed with distilled water and brine. The obtained organic layer was dried over Na 2 SO 4 and filtered. The solvent in the filtrate was removed by evaporation and the residue was separated and purified by flash silica chromatography (n-hexane: EtOAc = 2: 1) to afford the title compound (195 mg).
Yield: 97.8%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.42 (m, 5H), 5.08 (dt, 1H, J = 8.4 and 6.9 Hz), 4.84 (dd, 1H, J = 8.7 6.8 Hz), 4.79 (br, 1H ), 4.46 (t, 1 H, J = 8.6 Hz);
13 C NMR (75 MHz, CDCl 3 ): δ 135.3, 129.6, 129.4, 126.7, 75.0, 59.6;
EIMS (70 eV) m / z (rel intensity): 199 (M +, 7), 169 (33), 104 (100);
[α] D 23 = −37.1 (c 0.70, CHCl 3 );
HPLC (Chiralcel ® AD-H column ( Daicel (Daicel), Inc.), isopropanol (iPrOH) / hexane (hexane) 15/85, 0.8 mL / min): t1 = 11.7 bun (R), t2 = 13.2 bun (S );
ee = 98%.
< Example 2> (R) -4- (3- Methoxyphenyl ) -5H- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in place of the obtained in Preparation Example 2-3 4- (3-methoxyphenyl) -5H- [1, The title compound was prepared in the same manner as in Example 1, except that 2,3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Molecular weight: 229;
Yield: 88%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.32 (t, J = 7.8 Hz, 1H), 6.98-6.89 (m, 3H), 5.07-5.01 (m, 2H), 4.82 (t, J = 8.5 Hz, 1H), 4.42 (t, J = 8.5 Hz, 1H), 3.81 (s, 3H);
13 C NMR (75 MHz, CDCl 3 ): δ 160.2, 136.9, 130.5, 118.7, 114.9, 112.2, 75.1, 59.4, 55.4;
EIMS (70 eV) m / z (rel intensity): 229 (M +, 39), 134 (100), 105 (47), 77 (15), 65 (14);
[a] D 23 = -32.1 (c 0.29, CHC1 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 10.5 bun (R), t2 = 11.7 bun (S);
ee = 96%
< Example 3> (R) -4- (4- Methoxyphenyl ) -5H- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in place of the in Preparation Example 2-4 4- (4-methoxyphenyl) -5H- [1,2 The title compound was prepared in the same manner as in Example 1, except that 3,3-oxathiazole-2,2-dioxide (1 mmol) was used.
Molecular weight: 229;
Yield: 85%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.35 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 5.03 (q, J = 6.8 Hz, 1H), 4.79 (dd , J = 8.7 and 6.7 Hz, 1H), 4.64 (d, J = 6.2 Hz, 1H), 4.44 (t, J = 8.7 Hz, 1H), 3.82 (s, 3H);
13 C NMR (75 MHz, CDCl 3 ): δ 160.5, 128.2, 126.9, 114.7, 75.3, 59.3, 55.4;
EIMS (70 eV) m / z (rel intensity): 229 (M +, 4), 135 (100), 91 (12), 77 (18), 65 (60);
[α] D 23 = -34.4 (c 0.50, CHCl 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 11.0 bun (R), t2 = 12.7 bun (S);
ee = 97%.
< Example 4> (R) -4- (3- Chlorophenyl ) -5H- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-5, the dioxide instead of 4- (3-chlorophenyl) -5H- [1,2, The title compound was prepared in the same manner as in Example 1, except that 3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Molecular weight: 234;
Yield: 95%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 8.58 (d, J = 5.5 Hz, 1H), 7.53-7.52 (m, 1H), 7.49-7.40 (m, 3H), 5.17-5.11 (m, 1H ), 4.96 (dd, J = 8.7 and 7.0 Hz, 1H), 4.38 (dd, J = 8.7 and 6.9 Hz, 1H);
13 C NMR (75 MHz, DMSO-d 6 ): δ 140.2, 133.3, 130.6, 128.3, 126.6, 125.4, 74.6, 57.6;
EIMS (70 eV) m / z (rel intensity): 233 (M +, 6), 202 (12), 138 (100), 111 (16), 75 (19);
[α] D 23 = -33.6 (c 0.42, CHCl 3 );
HPLC (Chiralcel ® AD-H column (manufactured by Daicel Corporation), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 8.5 minutes (R), t2 = 9.4 minutes (S);
ee = 99%.
< Example 5> (R) -4- (4- Chlorophenyl ) -5H- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-6, the dioxide instead of 4- (4-chlorophenyl) -5H- [1,2, The title compound was prepared in the same manner as in Example 1, except that 3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Molecular weight: 234;
Yield: 81%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.43-7.35 (m, 4H), 5.06 (q, J = 6.9 Hz, 1H), 4.90 (d, J = 5.0 Hz, 1H), 4.84 (dd, J = 8.7 and 6.9 Hz, 1 H), 4.39 (t, J = 8.4 Hz, 1 H);
13 C NMR (75 MHz, CDCl 3 ): δ 135.5, 134.2, 129.6, 128.1, 74.6, 58.9;
EIMS (70 eV) m / z (rel intensity): 233 (M +, 10), 203 (14), 139 (100), 110 (13), 75 (14);
[a] D 23 = -31.9 (c 0.36, CHC1 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min) t1 = 8.9 bun (R), t2 = 11.3 bun (S);
ee = 95%
< Example 6> (R) -4- (4- Trifluoromethylphenyl ) -5H- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-7 in place of 4-dioxide (4-trifluoromethyl-phenyl) -5H- [1,2 The title compound was prepared in the same manner as in Example 1, except that, 3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Molecular weight: 267;
Yield: 76%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.71 (d, J = 8.2 Hz, 2H), 7.58 (d, J = 8.1 Hz, 2H), 5.16 (q, J = 7.4 Hz, 1H), 4.95 (br , 1H), 4.90 (dd, J = 8.8 and 7.2 Hz, 1H), 4.41 (dd, J = 8.8 and 7.8 Hz, 1H);
EIMS (70 eV) m / z (rel intensity): 267 (M +, 1), 139 (7), 111 (20), 97 (28), 71 (47), 57 (100);
[a] D 23 = -22.5 (c 0.44, CHC1 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 7.5 bun (R), t2 = 10.0 bun (S);
ee = 87%.
< Example 7> (R) -4- (2- Naphthyl ) -5H- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-8 in place of 4-dioxide (2-naphthyl) -5H- [1,2, The title compound was prepared in the same manner as in Example 1, except that 3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Example 249;
Yield: 85%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.93 (d, J = 8.6 Hz, 1H), 7.88-7.83 (m, 3H), 7.58-7.50 (m, 3H), 5.25 (q, J = 7.1 Hz, 1H), 4.91 (dd, J = 8.8 and 6.9 Hz, 1H), 4.79 (d, J = 6.2 Hz, 1H), 4.55 (t, J = 8.6 Hz, 1H);
13 C NMR (75 MHz, CDCl 3 ): δ 133.6, 133.1, 132.5, 129.7, 128.0, 127.9, 127.1, 127.0, 126.5, 123.3, 74.7, 59.8;
EIMS (70 eV) m / z (rel intensity): 249 (M +, 15), 155 (100), 127 (29), 77 (11);
[a] D 23 = -31.5 (c 0.36, CHC1 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 11.3 bun (R), t2 = 14.0 bun (S);
ee = 96%.
< Example 8> (R) -4- Phenyl -5,5-dimethyl- [1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-9 in place of 4-dioxide-5,5-dimethyl- [1,2,3 ] -Oxathiazole-2,2-dioxide (1 mmol) was used in the same manner as in Example 1, except that the title compound was prepared.
Molecular weight: 227;
Yield: 93%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.43-7.37 (m, 5H), 5.05-5.04 (m, 1H), 4.92 (d, J = 5.1 Hz, 1H), 1.67 (s, 3H), 1.25 ( s, 3H);
13 C NMR (75 MHz, CDCl 3 ): δ 133.2, 129.4, 128.9, 127.0, 94.4, 68.5, 26.4, 22.7;
EIMS (70 eV) m / z (relintensity): 227 (M < + >, 0.04), 104 (100), 77 (19);
[a] D 23 = -80.4 (c 0.45, CHC1 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 8.2 bun (R), t2 = 9.2 bun (S);
ee = 81%.
< Example 9> (S) -4- ( Furan -2-yl)-[1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-10 in-dioxide instead of 4- (furan-2-yl) -5H- [1,2 The title compound was prepared in the same manner as in Example 1 except for using 3,3-oxathiazole-2,2-dioxide (1 mmol).
Yield: 96.1%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.48 (dd, 1H, J = 1.8 and 0.7 Hz), 6.51 (d, 1H, J = 3.3 Hz), 6.42 (dd, 1H, J = 3.3 and 1.8 Hz) , 5.12 (q, 1H, J = 7.2 Hz), 4.79-4.63 (m, 3H);
13 C NMR (75 MHz, CDCl 3 ): δ 149.6, 143.7, 110.7, 109.0, 72.1, 52.1;
EIMS (70 eV) m / z (rel intensity): 189 (M +, 15), 159 (11), 95 (100);
[α] D 23 = -8.6 (c 0.25, CHCl 3 );
ee = 98%.
< Example 10> (S) -4- (thiophen-2-yl)-[1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in place of 4- (thiophen-2-yl) prepared in Preparation Example 2-11 in -5H- [1, The title compound was prepared in the same manner as in Example 1 except for using 2,3] -oxathiazole-2,2-dioxide (1 mmol).
Yield: 97.0%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.40 (dd, 1H, J = 5.1 and 1.2 Hz), 7.21-7.13 (m, 1H), 7.05 (dd, 1H, J = 5.1 and 3.6 Hz), 5.34 ( q, 1H, J = 6.6 Hz), 4.85 (dd, 1H, J = 8.7 and 6.6 Hz), 4.83 (br, 1H), 4.56 (t, 1H, J = 8.6 Hz);
13 C NMR (75 MHz, CDCl 3 ): δ 137.3, 127.6, 127.2, 127.1, 75.3, 55.4;
EIMS (70 eV) m / z (rel intensity) 205 (M +, 19), 175 (24), 111 (100);
[α] D 23 = -7.4 (c 0.67, CHCl 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 15/85, 0.8 mL / min): t1 = 13.7 bun (R), t2 = 14.9 bun (S);
ee = 99%.
< Example 11> (R) -4- (pyridin-3-yl)-[1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-14 in-dioxide instead of 4- (pyridin -3 yl) -5H- [1,2, The title compound was prepared in the same manner as in Example 1, except that 3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Yield: 90.6%;
1 H NMR (300 MHz, CD 3 OD): δ 8.64 (d, 1H, J = 2.3 Hz), 8.54 (dd, 1H, J = 4.9 and 1.6 Hz), 8.02-7.98 (m, 1H), 7.49 (ddd , 1H, J = 8.0 and 4.9 and 0.6 Hz), 5.16 (t, 1H, J = 7.0 Hz), 4.96 (dd, 1H, J = 8.8 and 7.1 Hz), 4.41 (dd, 1H, J = 8.8 and 6.8 Hz);
13 C NMR (75 MHz, CD 3 OD): δ 150.3, 148.9, 136.7, 140.0, 125.5, 75.6, 58.0;
EIMS (70 eV) m / z (rel intensity): 200 (M +, 9), 170 (26), 106 (100);
[α] D 23 = poor solubility, unable to measure;
HPLC (Chiralcel ® AD-H column (manufactured by Daicel Corporation), iPrOH / hexane 15/85, 0.8 mL / min): t1 = 14.2 min (R), t2 = 16.6 min (S);
ee = 99%.
< Example 12> (S) -4- ( Benzofuran -2-yl)-[1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in place of a produced in Production Example 2-12 4- (benzofuran -2 days) -5H- [1,2 The title compound was prepared in the same manner as in Example 1 except for using 3,3-oxathiazole-2,2-dioxide (1 mmol).
Yield: 83.3%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.59 (d, 1H, J = 7.6 Hz), 7.49 (d, 1H, J = 8.5 Hz), 7.36 (td, 1H, J = 7.3 and 1.4 Hz), 7.27 (td, 1H, J = 7.5 and 1.0 Hz), 6.89 (s, 1H), 5.23 (q, 1H, J = 7.4 Hz), 4.94 (d, 1H, J = 7.3 Hz), 4.85 (dd, 1H, J = 8.6 and 8.8 Hz), 4.76 (dd, 1H, J = 8.4 and 7.7);
13 C NMR (75 MHz, CDCl 3 ): δ 155.2, 149.4, 127.3, 125.6, 123.6, 121.7, 111.5, 107.0, 72.7, 53.7;
EIMS (70 eV) m / z (rel intensity): 239 (M +, 29), 145 (100);
[a] D 23 = -23.0 (c 0.50, CHCl 3 );
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 15/85, 0.8 mL / min): t1 = 12.0 bun (R), t2 = 14.0 bun (S);
ee = 98%.
< Example 13> (R) -4- ( Benzothiophene -3-yl)-[1,2,3]- Oxathiazolidine -2,2- Dioxide
4--5 H - [1,2,3] - oxazole-2,2-thiazole prepared in Preparation Example 2-13 in-dioxide instead of 4- (benzothiophen-3-yl) -5H- [1 The title compound was prepared in the same manner as in Example 1, except that 2,3] -oxathiazole-2,2-dioxide (1 mmol) was used.
Yield: 30.0%;
1 H NMR (300 MHz, DMSO-D 6 ): δ 8.56 (d, 1H, J = 6.8 Hz), 8.09-7.93 (m, 2H), 7.87 (d, 1H, J = 0.7 Hz), 7.50-7.39 ( m, 2H), 5.48 (qd, 1H, J = 6.9 and 0.9 Hz), 5.08 (dd, 1H, J = 8.6 and 6.8 Hz), 4.65 (dd, 1H, J = 8.6 and 7.2 Hz);
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 15/85, 0.8 mL / min): t1 = 15.3 bun (R), t2 = 16.5 bun (S);
ee = 98%.
< Example 14> (R) -3- Phenyl -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide prepared in Preparation Example 2-15 in place of the 3-phenyl -1,2,5- thiadiazol sleepy -1, The title compound was prepared in the same manner as in Example 1, except that 1-dioxide (1 mmol) was used.
Yield: 91.9%
1 H NMR (300 MHz, CDCl 3 ): δ 7.38 (m, 5H), 4.94 (q, 1H, J = 6.3 Hz), 4.65 (d, 1H, J = 5.8 Hz), 4.59 (t, 1H, J = 6.4 Hz), 3.89 (dt, 1H, J = 11.8 and 6.6 Hz), 3.50 (dt, 1H, J = 11.7 and 7.8 Hz);
13 C NMR (75 MHz, CDCl 3 ): δ 137.7, 129.2, 128.9, 126.4, 61.3, 51.8;
EIMS (70eV) m / z (rel intensity) (M +,) No molecular ion peak
[a] D 23 = -49.2 (c 0.59, MeOH);
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 13.2 bun (R), t2 = 15.1 bun (S);
ee = 98%.
< Example 15> (R) -3- (3- Methoxyphenyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (3-methoxyphenyl) prepared in Preparation Example 2-17 in -1,2,5- The title compound was prepared in the same manner as in Example 1, except that thiadiazolin-1,1-dioxide (1 mmol) was used.
Molecular Weight: 228.2682
Yield: 86%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.29 (t, 1H, J = 8.1 Hz), 6.97-6.96 (m, 2H), 6.87-6.84 (m, 1H), 4.96 (br, 1H), 4.91- 4,87 (m, 2H), 3.88-3.82 (m, 1H), 3.79 (s, 1H), 3.46-3.40 (m, 1H);
13 C NMR (75 MHz, CDCl 3 ): 159.9, 139.6, 130.1, 118.4, 113.9, 111.87, 61.07, 55.25, 51.52;
EIMS (70 eV) m / z (relintensity) 228 (M +, 7), 134 (100), 105 (43);
HRMS: calcd for C 9 H 12 N 2 0 3 S (M +) 228.0569, found: 228.0571
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 15.3 bun (R), t2 = 17.4 bun (S);
ee = 97%.
< Example 16> (R) -3- (4- Methoxyphenyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (4-methoxyphenyl) prepared in Preparation Example 2-18 in -1,2,5- The title compound was prepared in the same manner as in Example 1, except that thiadiazolin-1,1-dioxide (1 mmol) was used.
Yield: 85%
1 H NMR (300 MHz, CDCl 3 ): δ 7.34 (d, 2H, J = 8.8 Hz), 6.93 (d, 2H, J = 8.6 Hz), 4.88 (dd, 1H, J = 14.0 and 6.5 Hz), 4.53 (d, 2H, J = 5.7 Hz), 3.89-3.77 (m, 3H), 3.82 (s, 3H), 3.49 (dt, 1H, J = 11.7 and 8.1 Hz);
13 C NMR (75 MHz, CD 3 OD): δ 161.1, 132.8, 128.9, 115.1, 62.1, 55.7, 52.6;
[α] D 21 = -43.7 ( c 0.27, MeOH);
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 30/70, 0.8 mL / min): t1 = 10.4 bun (S), t2 = 12.1 bun (R);
ee = 98.0%.
< Example 17> (R) -3- (3- Chlorophenyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (3-chlorophenyl) prepared in Preparation Example 2-19 in thiazol -1,2,5- The title compound was prepared in the same manner as in Example 1, except that diazoline-1,1-dioxide (1 mmol) was used.
Molecular weight: 233;
Yield: 81%;
1 H NMR (300 MHz, DMSO-d 6 ): δ 7.63 (br, 1H), 7.49 (t, J = 1.8 Hz, 1H), 7.43-7.34 (m, 3H), 7.18 (br, 1H), 4.80 ( t, J = 6.8 Hz, 1H), 3.80-3.74 (m, 1H), 3.09-3.03 (m, 1H);
EIMS (70 eV) m / z (rel intensity): 233 (M +, 1), 138 (100), 111 (19), 77 (24);
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 10.7 bun (R), t2 = 12.7 bun (S);
ee = 96.9%.
< Example 18> (R) -3- (4- Chlorophenyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (4-chlorophenyl) prepared in Preparation Example 2-20 in thiazol -1,2,5- The title compound was prepared in the same manner as in Example 1, except that diazoline-1,1-dioxide (1 mmol) was used.
Molecular Weight: 232.6873
Yield: 67%,
1 H NMR (300 MHz, CDCl 3 ): δ 7.41-7.35 (m, 4H), 4.92 (q, 1H, J = 6.4 Hz), 4.64 (br, 1H), 4.50 (br, 1H), 3.94-3.85 ( m, 1H), 3.49-3.40 (m, 1H);
13 C NMR (75 MHz, CDCl 3 ): 136.4, 134.6, 129.3, 127.6, 60.4, 51.5;
EIMS (70 eV) m / z (relintensity) 232 (M +, 0.1), 138 (100), 112 (16), 75 (14);
Positive-ion FAB-MS m / z 233 ([M + H] +, 37)
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 12.0 bun (R), t2 = 16.2 bun (S);
ee = 98%.
< Example 19> (R) -3- (4- Trifluoromethylphenyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in place of 3 prepared in Preparation Example 2-21 a (4-trifluoromethylphenyl) -1,2,5 The title compound was prepared in the same manner as in Example 1, except that -thiadiazolin-1,1-dioxide (1 mmol) was used.
Molecular weight: 266;
Yield: 73%
1 H NMR (300 MHz, DMSO-d 6 ): δ 7.62 (dd, J = 32.3 and 8.3 Hz, 4H), 7.68 (d, J = 6.7 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H) , 4.90 (q, J = 6.5 Hz, 1H), 3.85-3.77 (m, 1H), 3.13-3.04 (m, 1H);
EIMS (70 eV) m / z (rel intensity): 266 (M +, 1), 172 (67), 144 (16), 63 (25), 56 (45);
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t 1 = 8.8 bun (R), t 2 = 13.1 bun (S);
ee = 97.3%.
< Example 20> (R) -3- (2- Naphthyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (2-naphthyl) thiazole prepared in Preparation Example 2-22 in -1,2,5- The title compound was prepared in the same manner as in Example 1, except that diazoline-1,1-dioxide (1 mmol) was used.
Molecular weight: 248;
Yield: 77%;
1 H NMR (300 MHz, CDCl 3 ): δ 7.92-7.83 (m, 4H), 7.55-7.48 (m, 3H), 5.10 (q, J = 6.6 Hz, 1H), 4.65 (d, J = 5.9 Hz, 1H), 4.49 (t, J = 6.9 Hz, 1H), 4.00-3.91 (m, 1H), 3.64-3.55 (m, 1H);
EIMS (70 eV) m / z (rel intensity): 248 (M +, 3), 155 (100), 127 (25), 77 (7);
HPLC (Chiralcel ® AD-H column ( Daicel Co.), iPrOH / hexane 20/80, 0.8 mL / min): t1 = 15.1 bun (R), t2 = 20.3 bun (S);
ee = 94%.
< Example 21> (S) -3- (2- Furyl ) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide in place of a produced in Production Example 2-23 3- (furan-2-yl) -1,2,5- The title compound was prepared in the same manner as in Example 1, except that thiadiazolin-1,1-dioxide (1 mmol) was used.
Yield: 86.7%
1 H NMR (300 MHz, CDCl 3 ): δ 7.44 (dd, 1H, J = 1.8 and 0.8 Hz), 6.47-6.34 (m, 2H), 4.94 (t, 1H, J = 6.0 Hz), 4.65 (s , 2H), 3.89-3.61 (m, 2H);
13 C NMR (75 MHz, CDCl 3 ): δ 149.8, 143.5, 110.8, 109.0, 55.4, 49.2;
[α] D 22 = -1.2 ( c 0.45, CHC1 3 ).
< Example 22> (S) -3- (thiophen-2-yl) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (thiophen-2-yl) prepared in Preparation Example 2-24 in -1,2,5 The title compound was prepared in the same manner as in Example 1, except that -thiadiazolin-1,1-dioxide (1 mmol) was used.
Yield: 92.8%
1 H NMR (300 MHz, CDCl 3 ): δ 7.34 (dd, 1H, J = 5.1 and 1.2 Hz), 7.16-7.10 (m, 1H), 7.02 (dd, 1H, J = 5.1 and 3.6 Hz), 5.17 (q, 1H, J = 6.4 Hz), 4.66 (s, 2H), 3.91 (dt, 1H, J = 12.0 and 6.6 Hz), 3.61 (dt, 1H, J = 11.8 and 7.5 Hz);
13 C NMR (75 MHz, CDCl 3 ): δ 140.5, 127.5, 126.3, 126.0, 57.4, 52.2;
[α] D 23 = -8.8 ( c 0.45, CHCl 3 );
HPLC (Chiralcel ® AD-H column (manufactured by Daicel Corporation), iPrOH / hexane 15/85, 0.8 mL / min): t 1 = 22.7 min (R), t 2 = 24.2 min (S);
ee = 98.4%.
< Example 23> (S) -3- ( Benzofuran -2-yl) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (benzofuran-2-yl) prepared in Preparation Example 2-25 in -1,2,5 The title compound was prepared in the same manner as in Example 1, except that -thiadiazolin-1,1-dioxide (1 mmol) was used.
Yield: 86.6%
1 H NMR (300 MHz, CDCl 3 ): δ 7.57 (d, 1H, J = 7.8 Hz), 7.47 (d, 1H, J = 7.6 Hz), 7.37-7.21 (m, 2H), 6.85 (s, 1H ), 5.07 (q, 1H, J = 6.0 Hz), 4.73 (d, 1H, J = 6.3 Hz), 6.85 (s, 1H, J = 7.7 Hz), 3.96-3.76 (m, 2H);
13 C NMR (75 MHz, CD 3 OD): δ 156.7, 156.6, 129.5, 125.6, 124.1, 122.2, 112.1, 105.7, 56.7, 49.3;
[α] D 23 = -32.0 ( c 0.30, MeOH);
HPLC (Chiralcel ® AD-H column (manufactured by Daicel Corporation), iPrOH / hexane 20/80, 0.8 mL / min): t 1 = 12.2 min (R), t 2 = 14.1 min (S);
ee = 90.1%.
< Example 24> (S) -3- (pyridin-3-yl) -1,2,5- Thiadiazolidine -1,1- Dioxide
4--5 H - [1,2,3] - thiazol-oxa-2,2-dioxide instead of 3- (pyridin-3-yl) prepared in Preparation Example 2-27 in -1,2,5- The title compound was prepared in the same manner as in Example 1, except that thiadiazolin-1,1-dioxide (1 mmol) was used.
Yield: 45.0%;
1 H NMR (300 MHz, CD 3 OD): δ 8.59 (d, 2H, J = 42.1 Hz), 8.00 (d, 1H, J = 8.0 Hz), 7.48 (dd, 1H, J = 7.6 and 4.9 Hz) , 4.97 (t, 1H, J = 6.6 Hz), 3.91 (dd, 1H, J = 11.8 and 7.0 Hz), 3.35-3.29 (m, 1H);
EIMS (70 eV) m / z (relintensity) 200 ([M + H] + , 4), 106 (100), 79 (35);
[a] D 27 = -46.1 ( c 0.17, MeOH);
HPLC (Chiralcel ® AD-H column (manufactured by Daicel Corporation), iPrOH / hexane 20/80, 0.8 mL / min): t 1 = 15.1 min (R), t 2 = 16.0 min (S);
ee = 70.3%.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is clearly understood that the same is by way of illustration and example only and is not to be taken by way of limitation, It is to be understood that the invention may be practiced within the scope of the appended claims.
Claims (10)
[Formula 1a]
[Chemical Formula 1b]
(2)
In this formula,
R 1 and R 2 are each independently hydrogen or an alkyl group of C 1-6 ,
X is O or NH,
Y is selected from the group consisting of phenyl group, naphthalenyl group, furyl group, thienyl group, benzofuryl group, benzothienyl group and pyridinyl group, wherein Y is halogen, C 1-6 alkyl group, C 1-6 haloalkyl, It may be substituted with a substituent selected from the group consisting of C 1-6 alkoxy group, C 7-24 aralkyloxy group and nitro group,
The rhodium compound catalyst is a compound having a structure of Formula 3a or 3b:
[Chemical Formula 3]
(3b)
In this formula,
Ph is a phenyl group and Ts is a tosyl group.
Y is phenyl, 2-furyl, 2-thienyl, 3-furyl, 3-thienyl, 2-benzofuryl, 2-benzothienyl, 3-benzofuryl, 3-benzothienyl, 2-pyridinyl, 1 selected from the group consisting of 3-pyridinyl and 4-pyridinyl, and selected from the group consisting of methyl, ethyl, methoxy, ethoxy, benzyloxy, fluoro, chloro, bromo, trifluoromethyl and nitro groups A method for producing a compound which can be substituted with at least one substituent.
The rhodium compound catalyst is used in an amount of 0.01 to 0.0001 mole per 1 mole of the compound of formula (2).
The compound of Formula 2, a-hydroxy ketone of the formula (4) is sulfamide, N, N ' -dimethyl sulfamide, N, N' -diethyl sulfamide, methyl sulfamate, ethyl sulfamate, 2,2 A process for producing a method comprising the step of reacting under a reflux or an acidic condition with sulfamide selected from the group consisting of 2-trichloroethyl sulfamate and mixtures thereof.
[Chemical Formula 4]
In this formula,
R 1 and R 2 are each independently hydrogen or an alkyl group of C 1-6 ,
Y is selected from the group consisting of phenyl group, naphthalenyl group, furyl group, thienyl group, benzofuryl group, benzothienyl group and pyridinyl group, wherein Y is halogen, C 1-6 alkyl group, C 1-6 haloalkyl, It may be substituted with a substituent selected from the group consisting of a C 1-6 alkoxy group, C 7-24 aralkyloxy group and nitro group.
A-hydroxy ketone of the formula (4) is 1-phenyl-2-hydroxyethanone, 1- (2-furyl) -2-hydroxyethanone, 1- (2-thienyl) -2-hydroxyethane On, 1- (3-furyl) -2-hydroxyethanone, 1- (3-thienyl) -2-hydroxyethanone, 1- (2-benzofuryl) -2-hydroxyethanone, 1 -(2-benzothienyl) -2-hydroxyethanone, 1- (3-benzofuryl) -2-hydroxyethanone, 1- (3-benzothienyl) -2-hydroxyethanone, 1 -(2-pyridinyl) -2-hydroxyethanone, 1- (3-pyridinyl) -2-hydroxyethanone, 1- (4-pyridinyl) -2-hydroxyethanone and mixtures thereof Manufacturing method characterized in that the selected from the group consisting of.
Wherein said acidic condition is selected from the group consisting of hydrochloric acid, hydrochloric anhydride, sulfuric acid, sulfuric anhydride, nitric acid, trifluoroacetic acid, trifluoromethanesulfonic acid, and mixtures thereof.
(2)
[Chemical Formula 4]
In this formula,
R 1 and R 2 are each independently hydrogen or an alkyl group of C 1-6 ,
X is O or NH,
Y is selected from the group consisting of phenyl group, naphthalenyl group, furyl group, thienyl group, benzofuryl group, benzothienyl group and pyridinyl group, wherein Y is halogen, C 1-6 alkyl group, C 1-6 haloalkyl, It may be substituted with a substituent selected from the group consisting of a C 1-6 alkoxy group, C 7-24 aralkyloxy group and nitro group.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20100058586A KR101286617B1 (en) | 2010-06-21 | 2010-06-21 | Method for preparing ［1,2,3］-oxathiazolidine-2,2-dioxide or ［1,2,5］-thiadiazolidine-1,1-dioxide derivatives |
| PCT/KR2011/004481 WO2011162514A2 (en) | 2010-06-21 | 2011-06-20 | Method for preparing [1,2,3]-oxathiazolidine-2,2-dioxide or [1,2,5]-thiadiazolidine-1,1-dioxide derivatives |
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| CN106608859B (en) * | 2015-10-21 | 2021-11-19 | 中国科学院上海药物研究所 | Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon |
| JP7073405B2 (en) * | 2017-05-03 | 2022-05-23 | ビーエーエスエフ ソシエタス・ヨーロピア | Method for Producing Chiral 2,3-Dihydrothiazolo [3,2-A] Pyrimidine-4-ium Compound |
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| WO2011162514A2 (en) | 2011-12-29 |
| KR20110138600A (en) | 2011-12-28 |
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