CN109456185A - Using N-Boc amide as the preparation method of Material synthesis ester type compound - Google Patents

Using N-Boc amide as the preparation method of Material synthesis ester type compound Download PDF

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CN109456185A
CN109456185A CN201811387347.0A CN201811387347A CN109456185A CN 109456185 A CN109456185 A CN 109456185A CN 201811387347 A CN201811387347 A CN 201811387347A CN 109456185 A CN109456185 A CN 109456185A
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雷川虎
叶丹锋
刘志园
陈闯
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University of Shanghai for Science and Technology
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    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
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    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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Abstract

The present invention relates to one kind withN- Boc amide is the preparation method of Material synthesis ester type compound, and this method is incited somebody to action using inorganic base as catalystNIntramolecular nucleophilic substitution reaction occurs for-Boc amide and various alcohol compounds, can be efficiently obtained various ester type compounds.This method has the advantages that reaction condition is mild, easy to operate, yield is high, functional group compatibility is good.

Description

Using N-Boc amide as the preparation method of Material synthesis ester type compound
Technical field
The present invention relates to one kindN- Boc amide is the preparation method of Material synthesis ester type compound, and especially one kind is to have There is torsion structure featureN- Boc amide is the preparation method of Material synthesis ester type compound.
Background technique
Amide is advantage functional group indispensable in organic synthesis, while being widely present in medicine, pesticide and function material Expect in molecule.In view of amides compound is almost used for the every field of chemistry, therefore, the selective chemical based on amide turns Change undoubtedly occupies highly important status in organic synthesis.Nevertheless, compared with acyl chlorides, acid anhydrides, ester, since amide resonates The presence of structure makes amide chemical property relative inertness, therefore amide is seldom used as the electrophilic reagent in organic reaction.Pass through Adjusting to substituent group in amide nitrogen atom destroys lone pair electrons on nitrogen-atoms and becomes tool torsion structure to the conjugation of carbonyl The amide of elephant.From 2015, the study groups such as Garg, Szostak reported nickel catalysis amide in succession and alcohol, ammonia, organic boron try Coupling reaction between agent, organic zinc reagent efficiently constructs a series of esters, amide and ketone compounds, referring to following reference Document:
(a) Liu, C.; Szostak, M. Chem. Eur. J.2017, 23, 7157。
(b) Hie, L; Fine Nathel, N. F.; Shah, T. K.; Baker, E. L.; Hong, X.; Yang, Y. –F.; Liu, P.; Houk, K. N.; Garg, N. K. Nature,2015, 524, 79。
But but there are severe reaction conditions, energy consumption height, need inert gas shielding, catalyst price high in the above method It is expensive, operation is complicated, be unfavorable for large-scale production etc. limitation.
Similar with amide, ester group is also one of very important basic functional group in organic chemistry, except traditional Fischer Esterification, acid are reacted with alcohol Mitsunobu, outside Steglich esterification, in recent years, the esters synthetic method phase of a series of novel After the Study of synthesis method of development, ester be still the hot spot of organic chemistry filed, referring to following bibliography:
(a)Sakakura, A.; Kawajiri, K.;Ohkubo, T.;Kosugi, Y.;Ishihara, K.J. Am. Chem. Soc.2007, 129, 14775；
(b) Dev, D.;Palakurthy, N. B.; Thalluri, K.;Chandra, J.; Mandal, B.J. Org. Chem., 2014, 79, 5420；
(c) Kim, Y.-H.; Han, J.; Jung, B. Y.; Baek, H.; Yamada, Y. M. A.; Uozumi, Y.; Lee, Y.-S. Synlett2016, 27, 29。
In conclusion developing general, the simple and direct esters chemical combination based on torsion amide for raw material using amide as electrophilic reagent Object synthetic method is meaningful research topic.
Summary of the invention
The object of the present invention is to provide a kind of universal synthesis methods of ester type compound.
In this method, nucleophilic substitution occurs for functionalized amides and alcohol, and reaction equation is as follows:
。
According to above-mentioned reaction mechanism, the present invention adopts the following technical scheme:
One kind withN- Boc amide is the preparation method of Material synthesis ester type compound, it is characterised in that the specific steps of this method Are as follows: it willN- Boc amide and alcohol are dissolved in dimethyl sulfoxide by the molar ratio of 1:1.5, add the inorganic salts and molecular sieve of catalytic amount, The reaction temperature is 0~120 DEG C；Methylene chloride extraction, saturated common salt water washing, organic phase is dry with anhydrous sodium sulfate, removal Solvent, then separating-purifying obtain ester type compound, structural formula are as follows:；DescribedNThe structure of-Boc amide Formula are as follows:；The structural formula of the alcohol are as follows:；Wherein R1Are as follows: alkyl, furans, the thiophene of C1~C12 Pheno, benzothiophene, alkenyl or the aromatic hydrocarbons containing substituent group；Substituent group in the aromatic hydrocarbons containing substituent group are as follows: C1~C6's At least one of alkyl, fluorine, chlorine, bromine, methoxyl group, trifluoromethyl, ester group, cyano or nitro；The R2Are as follows: C1~C12 Alkyl, cyclohexyl, benzhydryl, how fluorine-substituted alkyl, alkene replace alkyl, aliphatic heterocycle replace alkyl, furan It mutters alkyl, thiophene alkyl, aryl；The R3 is hydrogen atom, C1~C12 alkyl, benzyl, acyl group or sulfonyl.
Above-mentioned reaction temperature is 0 DEG C~80 DEG C, and the time is 2 hours~24 hours.
It is a kind of prepare it is above-mentioned withN- Boc amide is the method for Material synthesis ester type compound, it is characterised in that described Inorganic salts are as follows: Li2CO3、Na2CO3、K2CO3、Cs2CO3、K3PO4、LiO t Bu、NaO t Bu、KO t Bu、NaOAc、KOAc、CsF、 CsBr、CsOAc、HCOOCs、LiOH、NaOH、KOH。
Above-mentioned solvent are as follows: methylene chloride, toluene, dimethylbenzene, ether, tetrahydrofuran, ethyl acetate, n-hexane, Isosorbide-5-Nitrae- Dioxane, acetonitrile, dimethyl sulfoxide, n,N-Dimethylformamide or n,N-dimethylacetamide.
In above-mentioned preparation, shown in Formula II general structureN- Boc amides compound can be according to following sides reported in the literature Method is largely prepared: Wu, H., Guo, W. Daniel, S.; Li, Y.; Liu, C.; Zeng, Z.Chem. Eur.J. 2018, 24, 3444.
Raw material used in the present inventionN- Boc amide can be prepared largely, and catalyst valence is cheap and easy to get, and reaction condition is mild, be produced Rate is very high, and product is stable in the air and easily separated purifying, has a good application prospect.
Specific embodiment
The present invention is further elaborated combined with specific embodiments below, but the present invention is not limited to following embodiments.Institute State method is conventional method unless otherwise instructed.The reactant can obtain unless otherwise instructed from public commercial source.
Embodiment one: aromatic ester compound shown in preparation formula Ia general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 55.1 mg of compound, yield 89% shown in Formulas I a structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.4 , 2H), 7.57–7.53 (m, 1H), 7.44 (t, J = 7.6 Hz, 2H), 4.32 (t, J = 6.7 Hz, 2H), 1.80–1.75 (m, 2 H), 1.46– 1.43 (m, 2H), 1.36–1.33 (m, 4 H), 0.92–0.89 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ 166.8, 132.9, 129.7, 128.4, 65.3, 31.6, 28.8, 25.9, 22.7, 14.2.
GC-MS: Calcd for C13H18O2: 206.1; found: 206.0.
Embodiment two: aromatic ester compound shown in preparation formula Ib general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIb structural formulaN- Boc amide (97.6 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 52.8 mg of compound, yield 80% shown in Formulas I b structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 7.85 – 7.83 (m, 2H), 7.37 – 7.30 (m, 2H), 4.31 (t, J = 6.8 Hz, 2H), 2.40 (s, 3H), 1.80 – 1.73 (m, 2H), 1.46 – 1.42 (m, 2H), 1.36 – 1.31 (m, 4H), 0.89 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 167.0, 138.2, 133.7, 130.6, 130.2, 128.4, 126.8, 65.2, 31.6, 28.8, 25.9, 22.7, 21.4, 14.2.
GC-MS: Calcd for C14H20O2: 220.1; found: 220.0.
Embodiment three: aromatic ester compound shown in preparation formula Ic general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIc structural formulaN- Boc amide (97.6 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 50.5 mg of compound, yield 77% shown in Formulas I c structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 7.7 Hz, 2H), 4.29 (t, J = 6.6 Hz, 2H), 2.41 (s, 3H), 1.79 – 1.72 (m, 2H), 1.46 – 1.42 (m, 2H), 1.36 – 1.32 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 166.9, 143.5, 129.7, 129.2, 127.9, 65.1, 31.6, 28.8, 25.9, 22.7, 21.8, 14.2.
GC-MS: Calcd for C14H20O2: 220.1; found: 220.0.
Example IV: aromatic ester compound shown in preparation formula Id general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IId structural formulaN- Boc amide (85.3 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 54.2 mg of compound, yield 92% shown in Formulas I d structural formula.The product is solid.
1H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 9.6 Hz, 2H), 6.93 (d, J = 9.2 Hz, 2H), 4.28 (t, J = 6.8 Hz, 2H), 3.86 (s, 3H), 1.78 – 1.71 (m, 2H), 1.49 – 1.42 (m, 2H), 1.36 – 1.32 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H)
13C NMR (100 MHz, CDCl3): δ 166.6, 163.4, 131.7, 123.1, 113.7, 65.0, 55.5, 31.6, 28.9, 25.9, 22.7, 14.2.
GC-MS: Calcd for C14H20O3: 236.1; found: 236.0.
Embodiment five: aromatic ester compound shown in preparation formula Ie general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIe structural formulaN- Boc amide (111.3 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 70.4 mg of compound, yield 88% shown in Formulas I e structural formula.The product is solid.
1H NMR (400 MHz, CDCl3): δ 7.19 (d, J = 2.4 Hz, 2H), 6.65 – 6.64 (m, 1H), 4.30 (t, J = 6.1 Hz, 2H), 3.84 (s, 6H), 1.79 – 1.72 (m, 2H), 1.45 – 1.42 (m, 2H), 1.36 – 1.32 (m, 4H), 0.90 (t, J = 6.8 Hz, 3H)
13C NMR (100 MHz, CDCl3): δ 166.6, 160.7, 132.5, 107.3, 105.6, 65.5, 55.7, 31.6, 28.8, 25.8, 22.7, 14.2.
MS (ESI): Calcd for C15H22O4 [M+H]: 267.2; found: 267.2.
Embodiment six: aromatic ester compound shown in preparation formula If general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIf structural formulaN- Boc amide (98.7 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 44.6 mg of compound, yield 66% shown in Formulas I f structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.05 (dd, J = 9.0, 5.5 Hz, 2H), 7.11 (t, J = 8.7 Hz, 2H), 4.31 (t, J = 6Hz, 2H), 1.79 – 1.72 (m, 2H), 1.48 – 1.40 (m, 2H), 1.35 – 1.32 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 165.9, 165.8 (d, J = 252.2 Hz), 132.2 (d, J = 9.5 Hz), 126.9, 115.6 (d, J = 21.8 Hz) , 65.4, 31.6, 28.8, 25.8, 22.7, 14.2.
19F {1H} NMR (376 MHz, CDCl3): δ -106.0.
GC-MS: Calcd for C13H17FO2: 224.1; found: 224.0.
Aromatic ester compound shown in embodiment seven, preparation formula Ig general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIg structural formulaN- Boc amide (103.5 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 59.3 mg of compound, yield 82% shown in Formulas I g structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 9.2 Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 4.35 (t, J = 6.7, 2H), 1.79 – 1.72 (m, 2H), 1.45 – 1.42 (m, 2H), 1.36 – 1.32 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 166.0, 139.4, 131.1, 129.1, 128.8, 65.5, 31.6, 28.8, 25.8, 22.7, 14.2.
GC-MS: Calcd for C13H17ClO2: 240.1; found: 240.0.
Embodiment eight: aromatic ester compound shown in preparation formula Ih general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIh structural formulaN- Boc amide (116.7 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 71.5 mg of compound, yield 84% shown in Formulas I h structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 7.90 (d, J = 9.2 Hz, 2H), 7.58 (d, J = 7.6 Hz, 2H), 4.31 (t, J = 6.6 Hz, 2H), 1.79 – 1.72 (m, 2H), 1.49 – 1.42 (m, 2H), 1.36 – 1.32 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 166.1, 131.8, 131.2, 129.5, 128.0, 65.6, 31.6, 28.8, 25.8, 22.7, 14.2.
GC-MS: Calcd for C13H17BrO2: 284.0; found: 284.0.
Embodiment nine: aromatic ester compound shown in preparation formula Ii general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIi structural formulaN- Boc amide (113.7 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 62.4 mg of compound, yield 76% shown in Formulas I i structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.2 Hz, 2H), 4.35 (t, J = 6.7 Hz, 2H), 1.82 – 1.75 (m, 2H), 1.49 – 1.41 (m, 2H), 1.37 – 1.32 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 165.6, 134.5 (q, J = 32.4 Hz), 133.9 (q, J = 1.3 Hz), 130.1, 125.5 (q, J = 3.9 Hz), 123.8 (q, J = 273.3 Hz), 65.9, 31.6, 28.7, 25.8, 22.7, 14.1.
19F {1H} NMR (376 MHz, CDCl3): δ -63.0.
GC-MS: Calcd for C14H9F3O: 274.1; found: 274.0.
Embodiment ten: aromatic ester compound shown in preparation formula Ij general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIj structural formulaN- Boc amide (110.0 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 20.0 mg of compound, yield 25% shown in Formulas I j structural formula.
The product is solid.
1H NMR (400 MHz, CDCl3): δ 8.10 (s, 4H), 4.34 (t, J = 6.6 Hz, 2H), 3.95 (s, 3H), 1.82 – 1.76(m, 2H), 1.49 – 1.41 (m, 2H), 1.37 – 1.32 (m, 2H), 0.91 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 166.5, 166.0, 134.4, 133.9, 129.7, 129.6, 65.7, 52.6, 31.6, 28.7, 25.8, 22.6, 14.1.
MS (ESI): Calcd for C15H20O4[M+H]: 265.1; found: 265.1.
Embodiment 11: aromatic ester compound shown in preparation formula Ik general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIk structural formulaN- Boc amide (100.8 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 58.4 mg of compound, yield 78% shown in Formulas I k structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H), 4.35 (t, J = 6.7, 2H), 1.81 – 1.74 (m, 2H), 1.46 – 1.42 (m, 2H), 1.37 – 1.33 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 165.2, 134.4, 132.3, 130.2, 118.2, 116.4, 66.1, 31.5, 28.7, 25.8, 22.7, 14.1.
GC-MS: Calcd for C14H17NO2: 231.1; found: 231.0.
Embodiment 12: aromatic ester compound shown in preparation formula Il general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIl structural formulaN- Boc amide (106.8 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:40) elution of ethyl acetate and petroleum ether.It separates 66.0 mg of compound, yield 88% shown in Formulas I l structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 9.2 Hz, 2H), 8.21 (d, J = 8.8 Hz, 2H), 4.37 (t, J = 6.8 Hz, 2H), 1.83 – 1.76 (m, 2H), 1.47 – 1.44 (m, 2H), 1.37 – 1.34 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 164.9, 136.0, 130.8, 123.7, 66.3, 31.6, 28.7, 25.8, 22.7, 14.1.
GC-MS: Calcd for C13H17NO4: 251.1; found: 251.0.
Embodiment 13: aromatic ester compound shown in preparation formula Im general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIm structural formulaN- Boc amide (108.3 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 68.6 mg of compound, yield 89% shown in Formulas I m structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.61 (s, 1H), 8.07 (dd, J =8.6, 1.4 Hz, 1 H), 7.96 (d, J =8.0 Hz, 1 H), 7.88 (d, J = 8.5 Hz, 2H), 7.61 – 7.52 (m, 2H), 4.38 (t, J= 6.8 Hz, 2 H), 1.86 – 1.79 (m, 2 H), 1.51 – 1.45 (m, 2 H), 1.39 – 1.36 (m, 4 H), 0.94 – 0.90 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ 167.0, 135.6, 132.6, 131.1, 129.5, 128.3, 128.2, 127.90, 127.89, 126.7, 125.4, 65.5, 31.6, 28.9, 25.9, 22.7, 14.2.
GC-MS: Calcd for C17H20O2: 256.1; found: 256.0.
Embodiment 14: aromatic ester compound shown in preparation formula In general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIn structural formulaN- Boc amide (90.3 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 46.1 mg of compound, yield 78% shown in Formulas I n structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 7.58 – 7.57 (m, 1H), 7.18 – 7.16 (m, 1H), 6.52 – 6.50 (m, 1H), 4.30 (t, J = 6.7 Hz, 2H), 1.78 – 1.71 (m, 2H), 1.43 – 1.38 (m, 2H), 1.34 – 1.31 (m, 4H), 0.92 – 0.88 (m, 3H).
13C NMR (100 MHz, CDCl3): δ 159.0, 146.3, 145.0, 117.8, 111.9, 65.3, 31.6, 28.8, 25.7, 22.7, 14.1.
GC-MS: Calcd for C11H16O3: 196.1; found: 196.0.
Embodiment 15: aromatic ester compound shown in preparation formula Io general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIo structural formulaN- Boc amide (95.1 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 54.4 mg of compound, yield 85% shown in Formulas I o structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 7.80 (dd, J = 3.7, 1.3 Hz, 1H), 7.54 (dd, J = 5.0, 1.3 Hz, 1H), 7.10 (dd, J = 5.0, 3.7 Hz, 1H), 4.29 (t, J = 6.7 Hz, 2H), 1.80 – 1.72 (m, 2H), 1.45 – 1.40 (m, 2H), 1.36 – 1.32 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 162.5, 134.2, 133.3, 132.3, 127.8 , 65.4, 31.6, 28.8, 25.7, 22.7, 14.1.
GC-MS: Calcd for C11H16O2S: 212.1; found: 212.0
Embodiment 16: aromatic ester compound shown in preparation formula Ip general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIp structural formulaN- Boc amide (110.0mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 66.9 mg of compound, yield 85% shown in Formulas I p structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 7.89 – 7.85 (m, 2H), 7.47 – 7.38 (m, 2H), 4.34 (t, J = 6.7 Hz, 2H), 1.82 – 1.75 (m, 2H), 1.49 – 1.42 (m, 2H), 1.39 – 1.34 (m, 4H), 0.91 (t, J = 6.6 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 163.0, 142.3, 138.9, 134.0, 130.5, 127.0, 125.6, 125.0, 122.9, 65.9, 31.6, 28.8, 25.8, 22.7, 14.2.
MS (ESI): Calcd for C15H18O2S[M+H]: 263.1; found: 263.1.
Embodiment 17: ester type compound shown in preparation formula Iq general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIq structural formulaN- Boc amide (95.1 mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 49.9 mg of compound, yield 78% shown in Formulas I q structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 4.05 (t, J = 6.7 Hz, 2H), 2.28 (tt, J = 11.3, 3.6 Hz, 1H), 1.91 – 1.88 (m, 2H), 1.78 – 1.73 (m, 2H), 1.66 – 1.59 (m, 2H),1.48 – 1.19 (m, 12H), 0.89 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 176.4, 64.4, 43.4, 31.6, 29.2, 28.8, 25.9, 25.7, 25.6, 22.7, 14.1.
GC-MS: Calcd for C13H24O2: 212.2; found: 212.0
Embodiment 18: ester type compound shown in preparation formula Ir general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIr structural formulaN- Boc amide (326.6mg, 0.3 mmol), and alcohol shown in formula III a structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 76.4 mg of compound, yield 72% shown in Formulas I r structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.10 (s, 4H), 4.34 (t, J = 6.6 Hz, 4H), 1.82 – 1.76 (m, 4H), 1.50 – 1.41 (m, 4H), 1.37 – 1.32 (m, 8H), 0.91 (t, J = 7.2 Hz, 6H).
13C NMR (100 MHz, CDCl3): δ 166.1, 134.3, 129.6, 65.7, 31.6, 28.8, 25.8, 22.7, 14.2.
MS (ESI): Calcd for C20H30O4[M+H]: 335.2; found: 335.2.
Embodiment 19: aromatic ester compound shown in preparation formula Is general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III b structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 60 mg of compound, yield 91% shown in Formulas I s structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.08 – 8.06 (m, 2H), 7.58–7.54 (m, 1H), 7.46–7.42 (m, 2H), 4.41–4.36 (m, 1H), 4.31–4.26 (m, 2H), 3.97– 3.81 (m, 2H), 2.12–2.01 (m,1H), 2.00–1.88 (m, 2H), 1.76–1.69 (m, 1H).
13C NMR (100 MHz, CDCl3): δ 166.7, 133.1, 130.2, 129.8, 128.5, 76.7, 68.7, 67.1, 28.2,25.9.
GC-MS: Calcd for C12H14O3: 206.1; found:206.0.
Embodiment 20: aromatic ester compound shown in preparation formula It general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III c structural formula (58.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 55.9 mg of compound, yield 79% shown in Formulas I t structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.09 – 8.04 (m, 2H), 7.59–7.55 (m, 1H), 7.47 – 7.43 (m, 2H), 4.47 (t, J = 5.8 Hz, 2H), 3.74 – 3.71 (m, 4H), 2.78 (t,J = 5.9 Hz, 2H), 2.59 – 2.57 (m, 4H).
13C NMR (100 MHz, CDCl3): δ 166.6, 133.1, 130.3, 129.7, 128.5, 67.1, 62.5, 57.2, 54.0.
MS (ESI): Calcd for C13H17NO3: 236.1[M+H]; found: 236.1.
Embodiment 21: aromatic ester compound shown in preparation formula Iu general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III d structural formula (149.4 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 107.3 mg of compound, yield 82% shown in Formulas I u structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.09 – 8.06 (m, 2H), 7.65 – 7.60 (m, 1H), 7.51 – 7.46 (m, 2H), 6.06 (tt, J = 51.9, 5.2 Hz, 1H), 4.83 (t, J = 13.3 Hz, 2H).
13C NMR (100 MHz, CDCl3): δ 165.1, 134.1, 130.2, 128.8, 128.5, 60.5, 60.2, 60.0.
GC-MS: Calcd for C15H10 F12O: 436.0; found: 436.0.
Embodiment 22: aromatic ester compound shown in preparation formula Iv general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III e structural formula (69.0 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 54.8 mg of compound, yield 71% shown in Formulas I v structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.06 – 8.04 (m, 2H), 7.57 – 7.52 (m, 1H), 7.45 – 7.41 (m, 2H), 5.49 – 5.45 (m, 1H),5.11 – 5.08 (m, 1H), 4.85 – 4.83 (m, 2H),2.14 – 2.08 (m, 4H), 1.77 (s, 3H), 1.68 (s, 3H), 1.61 (s, 3H).
13C NMR (100 MHz, CDCl3):δ 166.8, 142.5, 132.9, 131.9, 130.6, 129.7, 128.4, 123.8, 118.5, 62.0, 39.7, 26.4, 25.8, 17.8, 16.7.
GC-MS: Calcd for C17H22O2: 258.2; found: 258.0.
Embodiment 23: aromatic ester compound shown in preparation formula Iw general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III f structural formula (52.3 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 54.3 mg of compound, yield 85% shown in Formulas I w structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3):δ 8.08 (d, J = 8.1 Hz, 2H), 7.57 – 7.53 (m, 1H), 7.47 – 7.32 (m, 7H), 5.36 (s, 2H).
13C NMR (100 MHz, CDCl3): δ 196.4, 137.4, 135.1, 133.7, 128.8, 128.7, 128.21, 128.15, 128.1, 73.5, 72.7.
GC-MS: Calcd for C14H12O2: 212.1; found: 212.0.
Embodiment 24: aromatic ester compound shown in preparation formula Ix general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III g structural formula (45.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 59.5 mg of compound, yield 91% shown in Formulas I x structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.07 – 8.04 (m, 2H), 7.54 (tt, J = 7.4, 1.4 Hz, 1H), 7.42 (t, J = 7.7 Hz, 2H), 7.33 (dd, J = 5.1, 1.2 Hz, 1H), 7.17– 7.16 (m, 1H), 7.00 (dd, J = 5.1, 3.5 Hz, 1H), 5.51 (s, 2H).
13C NMR (100 MHz, CDCl3): δ 166.4, 138.1, 133.2, 130.0, 129.9, 128.5, 128.3, 126.98, 126.95, 61.2.
GC-MS: Calcd for C12H10SO2: 218.0; found: 218.0.
Embodiment 25: aromatic ester compound shown in preparation formula Iy general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III h structural formula (45.0 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 48.3 mg of compound, yield 74% shown in Formulas I y structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3):δ 8.09 – 8.01 (m, 2H), 7.58 – 7.51 (m, 1H), 7.43 (m, 2H), 5.07 – 5.00 (m, 1H), 1.97 – 1.93 (m, 2H), 1.83 – 1.77 (m, 2H), 1.64 – 1.55 (m, 4H), 1.50 – 1.36 (m, 4H).
13C NMR (100 MHz, CDCl3): δ166.1, 132.8, 131.1, 129.7, 128.4, 73.2, 31.8, 25.6, 23.8.
GC-MS: Calcd for C14H12O2: 218.1; found: 218.0.
Embodiment 26: aromatic ester compound shown in preparation formula Iz general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3 mg, 0.3 mmol), and alcohol shown in formula III i structural formula (82.9 mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:30) elution of ethyl acetate and petroleum ether.It separates 55.0 mg of compound, yield 64% shown in Formulas I z structural formula.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.06 – 8.03 (m, 2H), 7.57 –7.52 (m, 1H), 7.45–7.41 (m, 2H), 5.29–5.23 (m, 1H), 1.88 –1.79 (m, 2H), 1.69 –1.62 (m, 2H), 149 –1.34 (m, 18H).
13C NMR (100 MHz, CDCl3): δ166.4, 132.8, 131.1, 129.7, 128.4, 73.1, 29.2, 24.3,24.1, 23.5, 23.3, 21.0.
GC-MS: Calcd for C19H28O2: 288.2; found: 288.0.
Embodiment 27: aromatic ester compound shown in preparation formula Iaa general structure
The reaction equation is as follows:
Specific preparation method is: under air conditions, sequentially adding magneton, formula into drying, 25 clean mL round-bottomed flasks Shown in IIa structural formulaN- Boc amide (93.3mg, 0.3 mmol), and alcohol shown in formula III j structural formula (82.8mg, 0.45 Mmol), Cs2CO3(19.5 mg, 0.06 mmol) adds dry 1.5 mL of DMSO of molecular sieve, reacts 24 h at room temperature. Methylene chloride extracts (25mL × 3 time), saturated common salt water washing, merges organic phase, and anhydrous sodium sulfate is dry.Filtrate rotary evaporation Except solvent, 200-300 mesh silica gel column chromatography after concentration, mixed solvent (1:40) elution of ethyl acetate and petroleum ether.It separates Compound 73.8mg shown in Formulas I aa structural formula, yield 85%.The product is liquid.
1H NMR (400 MHz, CDCl3): δ 8.16 – 8.13 (m, 2H), 7.59 – 7.55 (m, 1H), 7.48 – 7.42 (m, 6H), 7.37 – 7.33 (m, 4H), 7.31 – 7.27 (m, 2H), 7.12 (s, 1H).
13C NMR (100 MHz, CDCl3): δ 165.7, 140.4, 133.3, 129.9, 128.7, 128.6, 128.1, 127.26, 127.25, 77.6.
GC-MS: Calcd for C20H16O2: 288.1; found: 288.0.

Claims (4)

1. it is a kind of withN- Boc amide is the preparation method of Material synthesis ester type compound, it is characterised in that the specific step of this method Suddenly are as follows: willN- Boc amide and alcohol are dissolved in dimethyl sulfoxide by the molar ratio of 1:1.5, add the inorganic base and molecule of catalytic amount Sieve, the reaction temperature are 0~120 DEG C；Methylene chloride extraction, saturated common salt water washing, organic phase is dry with anhydrous sodium sulfate, goes Except solvent, then separating-purifying, ester type compound, structural formula are obtained are as follows:；DescribedNThe structure of-Boc amide Formula are as follows:；The structural formula of the alcohol are as follows:；Wherein R1Are as follows: alkyl, furans, the thiophene of C1~C12 Pheno, benzothiophene, alkenyl or the aromatic hydrocarbons containing substituent group；Substituent group in the aromatic hydrocarbons containing substituent group are as follows: C1~C6's At least one of alkyl, fluorine, chlorine, bromine, methoxyl group, trifluoromethyl, ester group, cyano or nitro；The R2Are as follows: C1~C12 Alkyl, cyclohexyl, benzhydryl, how fluorine-substituted alkyl, alkene replace alkyl, aliphatic heterocycle replace alkyl, furan It mutters alkyl, thiophene alkyl, aryl；The R3 is hydrogen atom, C1~C12 alkyl, benzyl, acyl group or sulfonyl.
2. according to the method described in claim 1, the time is 2 hours~24 small it is characterized in that reaction temperature is 0 DEG C~80 DEG C When.
3. it is a kind of prepare it is according to claim 1 withN- Boc amide is the method for Material synthesis ester type compound, feature It is the inorganic salts are as follows: Li2CO3、Na2CO3、K2CO3、Cs2CO3、K3PO4、LiO t Bu、NaO t Bu、KO t Bu、NaOAc、 KOAc、CsF、CsBr、CsOAc、HCOOCs、LiOH、NaOH、KOH。
4. according to the method described in claim 1, it is characterized in that the solvent are as follows: methylene chloride, toluene, dimethylbenzene, second Ether, tetrahydrofuran, ethyl acetate, n-hexane, Isosorbide-5-Nitrae-dioxane, acetonitrile, dimethyl sulfoxide, n,N-Dimethylformamide or N, N- dimethyl acetamide.
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