WO2001040163A1 - A PROCESS FOR PRODUCING AMINE COMPOUND WITH t-BUTOXYCARBONYL GROUP - Google Patents
A PROCESS FOR PRODUCING AMINE COMPOUND WITH t-BUTOXYCARBONYL GROUP Download PDFInfo
- Publication number
- WO2001040163A1 WO2001040163A1 PCT/KR2000/001371 KR0001371W WO0140163A1 WO 2001040163 A1 WO2001040163 A1 WO 2001040163A1 KR 0001371 W KR0001371 W KR 0001371W WO 0140163 A1 WO0140163 A1 WO 0140163A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- amine compound
- butoxycarbonylated
- organic solvent
- butylchloroformate
- butoxycarbonyl
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Definitions
- the cyclic amines are 3 to 8-membered cyclic amines containing a nitrogen atom.
- the solution was added 13.5 g (2 eq.) of sodium hydroxide. After slowly adding t- butylchloroformate obtained in Example 1, the solution was stirred for about 4 hours and subjected to phase separation. The aqueous layer was returned to the reactor and the pH value was controlled in the range from 1 to 2 with 35% HC1. The mixture was then extracted with 200 ml of ethylacetate. After phase separation, the organic solvent was dried over magnesium sulfate and removed from the organic layer through vacuum distillation to obtain yellowish oil. This oil was crystallized with n-hexane to obtain the pure title compound (80% yield).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Disclosed is a method for preparing a t-butoxycarbonylated amine compound and, more particularly, a method for preparing a t-butoxycarbonylated amine compound where an amine compound is reacted with a t-butylchloroformate in an aqueous organic solvent, the amine compound being selected from the group consisting of amines, represented by formula (I) RNH2 or (II) R1R2NH amino acids or amino alcohols thereof, or cylcic amines, where R, R1 and R2 are independently an aliphatic hydrocarbon, an aromatic hydrocarbon, or an alicyclic hydrocarbon. In the industrial production method for the T-butoxycarbonylated amine compound, a phosgene is reacted with an alkaline metal t-butoxide at a temperature of - 25 to - 10°C and the mixture is removed of an excess of phosgene by vacuum distillation to obtain a t-butylchloroformate solution, which is then reacted with the above amine compound in the presence of an organic solvent or an aqueous organic solvent at a temperature of -30 to 10°C, thereby readily producing the t-butoxycarbonylated amine compound at a relatively low cost.
Description
A process for producing amine compound with ."-butoxycarbonyl group
Technical Field
The present invention relates to a process for producing amine compound with t-butoxycarbonyl group and, more particularly, to a method for preparing a t- butoxycarbonylated amine compound with high yield where an amine compound is reacted with a t-butylchloroformate to produce a t-butoxycarbonyl(BOC)-protected amine compound.
Background Art
Some research teams have developed a protective BOC group as an amino protective group that may substitutes for the_ carbobenzoxy group of the amine compounds. For example, Carpino introduced the BOC group as a normal amino protective group (L.A. J. Am. Chem. Soc. 1957, 79, 98), and Mackay et al. proposed the use of the BOC group to protect the amino acids in the synthesis of peptides (J. Am. Chem. Soc. 1957. 79, 4686; and J. Am. Chem. Soc. 1957, 79, 6180). Compared to the conventional carbobenzoxy group, the BOC group is readily removable under weak acidic conditions and very stable to the catalytic hydrogenation. There have been developed many butoxycarbonylating agents for generating such an advantageous protective BOC group, including t- butylchloroformate, di-t-butyldicarbonate, t-butyloxycarbonylimidazol, and t- butyloxycarbonyloxysuccinic imide. Compared to the other butoxycarbonylating agents, t-butylchloroformate is
inexpensive and very useful commercially but unstable to moisture and temperature,
i.e., readily decomposed at 10 ° and susceptible to hydrolysis. For that reason, t- butylchloroformate is known not suitable for the industrial use. A. R. Choppin and J. W. Rogers suggested a method for preparing a BOC- protected amine compound where sodium butoxide was reacted with phosgene at -
60 °C to produce t-butylchloroformate with about 20% yield, which was then separated and reacted with an amine compound in an anhydrous organic solvent to yield the BOC-protected amine compound (J. Am. Chem. Soc. 1948, 70, 2967). To prepare the t-butylchloroformate, a diluted solution ofphosgene in a solvent is first cooled at a low temperature and slowly mixed with an alkaline metal /-butoxide, after which the mixture is filtered to remove inorganic substances and distilled under vacuum to remove the solvent. The t-butylchjoroformate thus obtained is then purified in a separate isolation and purification, step -with a- lot of loss, which leads to a low yield of the BOC-protected amine compound. That is, the preparation method suggested by A. R. Choppin et al. has a problem in that the yield of the BOC-protected amine compound is extremely loy. and that the reaction conditions are hard to control.
Disclosure of Invention
It is, therefore, an object of the present invention to provide a method for producing a BOC-protected amine compound with high yield using an inexpensive t-butylchloroformate as a butoxycarbonylating agent.
It is another object of the present invention to provide a method for producing a more readily BOC-protected amine compound.
To achieve the objects of the present invention, the inventors have made experiments by way of a react IR spectroscopy and surprisingly found that t- butylchloroformate is relatively stable at a low temperature and also reactive under the aqueous conditions.
Also, the inventors have studied to improve the problem with low production yield of the BOC-protected amine compound through isolation and purification of pure t-butylchloroformate and have contrived a method for preparing a BOC-protected amine compound with higher yield where an excess of phosgene is removed from the mixture by vacuum distillation to obtain a t-butylchloroformate solution, which is then immediately reacted with the amine compound without performing isolation and purification of the t-butylchloroformate.
According to the present invention as defined in claim 1, there is provided a method for preparing a t-butoxycarbonylated amine compound where an amine compound is reacted with a t-butylchloroformate in an aqueous organic solvent, the amine compound being selected from the group consisting of amines represented by the formula (I) or (II), amino acids or amino alcohols thereof, or cyclic amines, R H2 (I)
R,R2 H (II) where R, R, and R2 are independently an aliphatic hydrocarbon, an aromatic hydrocarbon, or an alicylic hydrocarbon.
Examples of the amino acids used herein include glycine, phenylglycine, alanine, phenylalanine, valine, leucine, isoleuciae, seriae, threonine, cysteine, cystine, methionine, arginine, aspartic acid, glutamic acid, hydroxyglutamic acid, roline, hydroxyproline, tyrosine, tryptophane, and histidine. The amino acids
include, if not specifically limited to, L- and D-forms of these amino acids.
Also, the cyclic amines are 3 to 8-membered cyclic amines containing a nitrogen atom.
Preferably, the reaction is conducted in the temperature range from -30 °C
to lO °C.
In the reaction between the amine compound and t-butylchloroformate, the amine compound being selected from the group consisting of amines represented by the formula (I) or (II), amino acids or amino alcohols thereof, or cyclic amines, examples of the aqueous organic solvent include aliphatic hydrocarbons such as normal hexane, pentane, butane and heptane; aliphatic ethers such as tetrahydrofurane, diethylether, dibutylether and dimethoxyethane; and aromatic hydrocarbons such as benzene and toluene. The mixing ratio of the organic solvent to water is preferably in the range from 1:9 to 9:1 in consideration of the expense of the organic solvent, although the higher mixing ratio of the organic solvent to water may result in the higher yield.
According to the present invention as defined in claim 7, there is provided a method for preparing a t-butoxycarbonylated amine compound where a phosgene is reacted with an alkaline metal t-butoxide and the mixture is removed of an excess of phosgene by vacuum distillation to obtain a t-butylchloroformate solution, which is then reacted with an amine compound, the amine compound being selected from the group consisting of amines represented by the formula (I) or (II), amino acids or amino alcohols thereof, or cyclic amines, RIMH2 (I) R,R2NH (II)
where R, R, and R2 are independently an aliphatic hydrocarbon, an aromatic hydrocarbon, or an alicyclic hydrocarbon.
In the above reaction, the phosgene is dissolved in the cooled organic solvent prior to the reaction with the alkaline metal t-butoxide. Examples of the organic solvent as used herein include aliphatic hydrocarbons such as normal hexane, pentane, butane and heptane; aliphatic ethers such as tetrahydrofurane, diethylether, dibutylether and dimethoxyethane; and aromatic hydrocarbons such as benzene and toluene. Examples of the alkaline metal t-butoxide as used herein include sodium t-butoxide, potassium t-butoxide and lithium t-butoxide. The reaction between phosgene and alkaline metal t-butoxide is conducted normally at a
temperature below -10 °C, and preferably in the range from -20 °C to -25 °C. The phosgene is used normally in an amount of 1 to 10 equivalent weights, and preferably 1.5 to 2.5 equivalent weights. In a reactor distinct from the reaction used for the preparation of the t- butylchloroformate solution, the amine compound is dissolved in a solvent that is the same as or different from the solvent used for the preparation of the t- butylchloroformate solution. The mixture is then cooled to below 0 °C. After
adding 1 to 3 equivalent weight of a base, the mixture is stirred in the temperature
range of 0 to 10 °C for 3 hours and water is added to dissolve all inorganic
substances, followed by phase separation. Subsequently, the organic layer is removed of the organic solvent through vacuum distillation to obtain the t- butoxycarbonylated amine compound.
The base used in the reaction between the t-butylchloroformate solution and
the amine compound can be selected from the groups consisting of inorganic bases (e.g., NaOH, KOH, Na2CO3) and organic bases (e.g., TEA). However, the reaction between the t-butylchloroformate solution and the amine compound can also be conducted in the absence of the base.
According to the present invention, the method for preparing the BOC- protected amine compound uses an inexpensive t-butylchloroformate as the starting material and applies the t-butylchloroformate in the slurry form to the preparation of the BOC-protected amine compound without a separate purification step of the t- butylchloroformate, thus simplifying the preparing process with an increase in the production yield.
Best Mode for Carrying Out the Invention
Hereinafter, the present invention will be described in detail by way of the following examples, which are not intended to limit the scope of the present invention.
Example 1 : Preparation of t-hutylchloroformate
200 ml of n-hexane was added to a 500ml four-necked reactor and cooled to
the internal temperature of -20 °C. After rapidly adding 30 g (1.5 eqJ) of phosgene,
20 g of sodium t-butoxide was slowly added over 1 hour. Then, the mixture was
stirred for about 1 hour in the internal temperature range from -25 °C to -20 °C. An excess of the phosgene was removed through vacuum distillation to obtain a t- butylchloroformate solution as white slurry. The solution was used in the subsequent reaction with amine.
Example 2: Preparation of t-butylchloroformate
The procedures were performed to obtain t-butylchloroformate in the same manner as Example 1 excepting that tetrahydrofurane was used as the organic solvent.
Example 3: Preparation of t-butylchloroformate
The procedures were performed to obtain t-butylchloroformate in the same manner as Example 1 excepting that toluene was used as the organic solvent.
Example 4: Preparation of t-hutylchloroformate The procedures were performed to obtain t-butylchloroformate in the same manner as Example 1 excepting that dimethoxyethane was used as the organic solvent.
Example 5: Preparation of t-butylcarbamate
50 ml of 20% aqueous ammonia solution was added to a 500ml four-necked
reactor and cooled to the internal temperature of 0 °C. After slowly adding t- butylchloroformate obtained in Example 1, the mixture was stirred for about 1 hour and subjected to separation into organic and aqueous layers. The organic solvent was removed from the organic layer through vacuum distillation to obtain t- butylcarbamate as a white solid (50% yield).
Melting point: 106 to 108 °C;
'H NMR (300 MHz, DMSO-dβ) 5I.45(9H, s, /-butyl) 4.70(2H, s, -NH2); and
IR(nujol) 3445, 3330, 3259, 3202, 3012, 2954, 1681, 1607, 1461, 1448,
1392, 1379 cm-1.
Example 6: Preparation of t-hutyl N-phenylcarhamate
100 ml of tetrahydrofurane and 38.7 g (2 eq.) of aniline were added to a
500ml four-necked reactor and cooled to 0 °C. After slowly adding t-
butylchloroformate obtained in Example 2, the mixture was stirred for about 1 hour and 100 ml of water was added. After stirring and phase separation of the mixed solution, the organic solvent was removed from the organic layer through vacuum distillation to obtain a straw-colored solid. The solid was then recrystallized to obtain pure t-butyl N-phenylcarbamate (80% yield).
Melting point: 136 °C;
Η MR (300 MHz, DMSO-d6) δl.45(9H, s, t-butyl) 6.946(1H, t, aromatic), 7.267(2H, q, aromatic), 7.46(m, 2H, aromatic); and
IR(nujol) 3313, 2929, 2858, 2596, 2013, 1690, 1649, 1460 cm 1.
Example 7: Preparation of 2-cyano-l-fN-t-butoxycarbonynethylaminoacetic acid eτhylester
100 ml of toluene and 16.5 g (0.5 eq.) of (2-cyanoethylamon)acetic acid
were added to a 500ml four-necked reactor and cooled to 0 °C. After slowly adding
t-butylchloroformate obtained in Example 3, the mixture was stirred for about 4 hours and the completion of the reaction was checked by the thin layer chromatography. 100 ml of water was added to the mixture and, after phase separation, the organic solvent (toluene) was removed from the orgamc layer through vacuum distillation to obtain the title compound as yellowish oil (80%
yield).
Η NMR (300 MHz, CDCL3) δl.5(9H, s, t-butyl) 4.2(2H, q), 3.48(2H, s),
2.96(2H, t), 2.54(2H, t), 1.3(3H, t); and
IR(neat) 2975, 2939, 2248, 1741, 1695, 1497, 1395, 1370 cm 1.
Example 8: Preparation of 4-rN-t-hutoxycarbonynaminomethylene-l-fN-t- butoxycarbonyl)pyrrolidine-3-one
25 g (0.7 eq.) of 4-aminomethylene-l-(N-t-butoxycarbonyl)pyrrolidine-3- one was added to a 500ml four-necked reactor and dissolved in 100 ml of
dimethoxyethane and 35 ml of water. The solution was cooled to 0 °C and 13.7 g (1
eq.) of potassium hydroxide was added. After slowly adding t-butylchloroformate obtained in Example 4, the mixture was stirred for about 30 minutes and the completion of the reaction was checked by the HPLC. 120. mL of 10% HC1 was added to the mixture and, after phase separation, the organic layer was returned to the reactor. Crystallization with IPA and water provided the pure title compound (60% yield).
Melting point: 138 to 162 °C;
Η NMR (300 MHz, CDCL3) δl.5(18H, s, t-butyl) 4.24QH, s, =CH-N),
4.30(2H, s, -CH2-), 4.32(2H, s, -CH2-); and
IR(nujol) 3252, 3175, 2914, 1731, 1720, 1697, 1608 cm 1.
Example 9: Preparation of t-butylcarbazate 11.3 ml (1 eq.) of 80% hydrazine and 100 ml of THF were added to a 500ml
four-necked reactor and cooled to 0 °C. After slowly adding t-butylchloroformate obtained in Example 2, the mixture was stirred for about 3 hours and 100 ml of water was added. Following the phase separation, the organic solvent was removed from the organic layer through vacuum distillation to obtain yellowish oil. This oil
was crystallized with n-hexane to obtain the pure title compound (70% yield).
Melting point: 38 to 40 °C;
Η NMR (300 MHz, CDCL3) 1.5(9H, s, t-butyl) δ; and IR(nujol) 3371, 3327, 3271, 3014, 2934, 1692, 1617, 1608-cm 1.
Example 10: Preparation ofN-(t-butylcarhonyl .-I.-alanine
15 g (0.168 mole) of L-alanine in 100 ml of water and 100 ml of an organic
solvent was added to a 500ml four-necked reactor and cooled to 0 °C. To the solution was added 13.5 g (2 eq.) of sodium hydroxide. After slowly adding t- butylchloroformate obtained in Example 1, the solution was stirred for about 4 hours and subjected to phase separation. The aqueous layer was returned to the reactor and the pH value was controlled in the range from 1 to 2 with 35% HC1. The mixture was then extracted with 200 ml of ethylacetate. After phase separation, the organic solvent was dried over magnesium sulfate and removed from the organic layer through vacuum distillation to obtain yellowish oil. This oil was crystallized with n-hexane to obtain the pure title compound (82% yield).
Melting point: 80 to 82 °C;
Η NMR (300 MHz, CDCL3) δl.42(3H, s, methyl), 1.5(9H, s, t-butyl); and
IR(nujol) 3380, 1736.5, 1690, 1525 cm-1. Example 11 : Preparation ofN-ft-bi.toxycarhonylV -phenylalanine
28 g (0.168 mole) of L-phenylalanine in 100 ml of water and 100 ml of an organic solvent was added to a 500ml four-necked reactor and cooled to 0 °C. To
the solution was added 13.5 g (2 eq.) of sodium hydroxide. After slowly adding t- butylchloroformate obtained in Example 1, the solution was stirred for about 4
hours and subjected to phase separation. The aqueous layer was returned to the reactor and the pH value was controlled in the range from 1 to 2 with 35% HC1. The mixture was then extracted with 200 ml of ethylacetate. After phase separation, the organic solvent was dried over magnesium sulfate and removed from the organic layer through vacuum distillation to obtain yellowish oil. This oil was crystallized with n-hexane to obtain the pure title compound (80% yield).
Melting point: 86 to 88 °C;
Η NMR (300 MHz, CDCL,) δl.281(s, butyl), 1417(s, t-butyl), 2.908, 3.083, 3.19, 4.398, 4.622, 4.99, 6.59, 7.29-7.19, 11.2; and
IR(nujol) 3315, 3101, 3091, 1712, 1649, 1606 cm 1. Example 12: Preparation of N-(t-butoxycarbonyl)-imidazol 11.5 g (0.168 mole) of imidazol and 100 ml of tetrahydrofurane were added to a 500ml four-necked reactor. Then, 17 g (0.168 mole) of triethylamine was added
to the mixture and cooled to 0 °C. After slowly adding t-butylchloroformate
obtained in Example 2, the solution was stirred for about 4 hours and subjected to phase separation. The organic solvent was removed from the organic layer through vacuum distillation and the residual was subjected to crystallization with n-hexane to yield the pure title compound (80% yield).
Melting point: 147 to 150 °C.
Industrial Applicability
The method for preparing a t-butoxycarbonylated amine compound according to the present invention is very effective in the industrial aspect in that
inexpensive t-butylchloroformate is used under readily controlled reaction conditions to produce the t-butoxycarbonylated amine compound with high yield.
Claims
1. A method for preparing a t-butoxycarbonylated amine compound,
wherein an amine compound is reacted with a t-butylchloroformate in an aqueous organic solvent, the amine compound being selected from the group consisting of amines represented by the formula (I) or (II), amino acids or amino alcohols thereof, or cyclic amines,
RNH2 (I)
R,R2NH (II) wherein R, R, and R2 are independently an aliphatic hydrocarbon, an aromatic hydrocarbon, or an alicyclic hydrocarbon.
2. The method as claimed in claim 1, wherein the aqueous organic solvent includes water and an organic solvent at a mixing ratio of 1 :9 to 9: 1.
3. The method as claimed in claim 1 or 2, wherein the reaction is
conducted in the temperature range from -30 °C to 10 °C.
4. The method as claimed in claim 1 or 2, wherein the t- butoxycarbonylated amine compound produced is 2-cyano-l-(N-t- butoxycarbonyl)ethylaminoacetic acid ethylester.
5. The method as claimed in claim 1 or 2, wherein the t- butoxycarbonylated amino acids or amino alcohols produced is 2-cyano-l-(N-t- butoxycarbonyl)ethy!aminoacetic acid ethylester.
6. The method as claimed in claim 1 or 2, wherein the t- butoxycarbonylated cyclic amine compound produced is 4-(N-t- butoxycarbonyl)aminomethylene- 1 -(N-t-butoxycarbonyl)pyrrolidine-3-one, or N-(t- butoxycarbonyl)-imidazol.
7. A method for preparing a t-butoxycarbonylated amine compound wherein a phosgene is reacted with an alkaline metal t-butoxide and the mixture is removed of an excess of phosgene by vacuum distillation to obtain a t- butylchloroformate solution, which is then reacted with an amine compound, the amine compound being selected from the group consisting of amines represented by the formula (I) or (II), amino acids or amino alcohols thereof, or cyclic amines, RNH2 (I)
R,R2NH (II) wherein R, R, and R2 are independently an aliphatic hydrocarbon, an aromatic hydrocarbon, or an alicyclic hydrocarbon.
8. The method as claimed in claim 7, wherein the reaction between the phosgene and the alkaline metal t-butoxide is conducted at a temperature of -25
to -10 °C.
9 The method as claimed in claim 7 or 8, wherein the reaction between the t-butylchloroformate and the amine compound is conducted in an aqueous organic solvent.
10. The method as claimed in claim 9, wherein the reaction is
conducted at a temperature of -30 to 10 °C.
11. The method as claimed in claim 9, wherein the aqueous organic solvent includes water and an organic solvent at a mixing ratio of 1 :9 to 9: 1.
12. The method as claimed in claim 9, wherein the reaction is conducted in the presence of a base.
13. The method as claimed in claim 7, wherein the t- butoxycarbonylated amine compound produced is 2-cyano-l-(N-t- butoxycarbonyl)ethylaminoacetic acid ethylester.
14. The method as claimed in claim 7, wherein the t- butoxycarbonylated cyclic amine compound produced is 4-(N-t- butoxycarbonyl)aminomethylene-l-(N-t-butoxycarbonyl)pyrrolidine-3-one, or N-(t- butoxycarbonyl)-imidazol.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019990054319A KR20010053806A (en) | 1999-12-01 | 1999-12-01 | A process for producing cyclicamine with t-Butoxycarbonyl group |
| KR1019990054318A KR20010053805A (en) | 1999-12-01 | 1999-12-01 | A process for producing amino acid or aminoalcohol with t-Butoxycarbonyl group |
| KR1999/54319 | 1999-12-01 | ||
| KR1019990054316A KR20010053804A (en) | 1999-12-01 | 1999-12-01 | A process for producing amine with t-Butoxycarbonyl group |
| KR1999/54318 | 1999-12-01 | ||
| KR1999/54316 | 1999-12-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2001040163A1 true WO2001040163A1 (en) | 2001-06-07 |
Family
ID=27350102
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2000/001371 WO2001040163A1 (en) | 1999-12-01 | 2000-11-28 | A PROCESS FOR PRODUCING AMINE COMPOUND WITH t-BUTOXYCARBONYL GROUP |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2001040163A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911084A (en) * | 2012-09-25 | 2013-02-06 | 浙江工业大学 | Preparation method of tert-butyl carbazate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4045433A (en) * | 1974-05-29 | 1977-08-30 | Richter Gedeon Vegyeszeti Gyar Rt. | 1,3,4,5-Tetrahydro-2H-1,4-benzodiazepin-2-ones |
| JPS6136261A (en) * | 1984-07-27 | 1986-02-20 | Hidehiko Watanabe | Novel carbonic acid ester compound and preparation thereof |
-
2000
- 2000-11-28 WO PCT/KR2000/001371 patent/WO2001040163A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4045433A (en) * | 1974-05-29 | 1977-08-30 | Richter Gedeon Vegyeszeti Gyar Rt. | 1,3,4,5-Tetrahydro-2H-1,4-benzodiazepin-2-ones |
| JPS6136261A (en) * | 1984-07-27 | 1986-02-20 | Hidehiko Watanabe | Novel carbonic acid ester compound and preparation thereof |
Non-Patent Citations (2)
| Title |
|---|
| CHOPPIN ET AL., J. AM. CHEM. SOC., vol. 70, 1948, pages 2967 * |
| SAKAKISBARA SHUMPEI ET AL., BULL. CHEM. SOC. JAP., vol. 42, no. 3, 1969, pages 809 - 811 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911084A (en) * | 2012-09-25 | 2013-02-06 | 浙江工业大学 | Preparation method of tert-butyl carbazate |
| CN102911084B (en) * | 2012-09-25 | 2014-03-26 | 浙江工业大学 | Preparation method of tert-butyl carbazate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU698239B2 (en) | Tachykinin antagonists | |
| FI102379B (en) | Urethane-protected amino acid N-carboxyanhydrides | |
| JP4803352B2 (en) | Process for producing amino acid-N-carboxyanhydride | |
| US8884009B2 (en) | Process for making bortezomib and intermediates for the process | |
| US20170369437A1 (en) | Process for Preparing Alpha-Carboxamide Pyrrolidine Derivatives | |
| Sureshbabu et al. | New and simple synthesis of acid azides, ureas and carbamates from carboxylic acids: application of peptide coupling agents EDC and HBTU | |
| JP2899327B2 (en) | New peptidase substrate analogs | |
| RU2498976C9 (en) | Improved method of producing dipeptidyl peptidase-iv inhibitor and intermediate compound | |
| JP2003073396A (en) | Method for manufacturing peptide | |
| WO2001040163A1 (en) | A PROCESS FOR PRODUCING AMINE COMPOUND WITH t-BUTOXYCARBONYL GROUP | |
| EP0562659B1 (en) | Process to synthetise peptides and new intermediates thereof | |
| SU1375123A3 (en) | Method of producing n-substituted l-amino acids | |
| JP2801500B2 (en) | Method for producing N-alkoxycarbonyl amino acid | |
| US20030181753A1 (en) | Method for producing amides or esters | |
| JPH0346460B2 (en) | ||
| JPH06340603A (en) | Alpha.- halo carboxylic acid ester | |
| KR20010053804A (en) | A process for producing amine with t-Butoxycarbonyl group | |
| US6670447B2 (en) | Amino acid N-carboxyanhydrides with acyl substituents on nitrogen atoms thereof | |
| KR20010053806A (en) | A process for producing cyclicamine with t-Butoxycarbonyl group | |
| US3445447A (en) | Tert-amyloxycarbonyl derivatives of amino acids | |
| KR20010053805A (en) | A process for producing amino acid or aminoalcohol with t-Butoxycarbonyl group | |
| KR102152445B1 (en) | Production method of intermediate compound for synthesizing medicament | |
| JPH078855B2 (en) | Sulfonium compound | |
| JP2000219683A (en) | Decarbamoylation of compound having n-carbamoyl protecting group, new carboxylic acid anhydride and use thereof | |
| WO2004037772A1 (en) | Convenient and scalable synthesis of ethyl n-[(2-boc-amino) ethyl] glycinate and its hydrochloride salt |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CN IN JP US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): CH DE ES FR GB IT |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: JP |