Method of synthesizing (1R,2R)-nitroalcohol compound

Patent metadata

Field	Value
Publication number	US-11623913-B2
Application number	US-202016830037-A
Country	US
Kind code	B2
Filing date	Mar 25, 2020
Priority date	Dec 11, 2019
Publication date	Apr 11, 2023
Grant date	Apr 11, 2023

Abstract

Disclosed is a method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme, including: subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), where R1 and R2 are defined in the same manner as that in the specification. The method involves mild reaction conditions, excellent diastereoselectivity and high chemical yield, and thus it is suitable for industrial applications.

First claim

What is claimed is:

1. A method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), comprising:
subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme:

wherein:
R 1 is hydrogen, methylsulfonyl, bromo, cyano, fluoro, methoxy, methylthio, methyl, trifluoromethyl, phenyl, acetoxy, or chloro; and
R 2 is hydrogen or tert-butyl dim ethyl silyl;
the chiral (1S,2R)-amino alcohol ligand is (1S,2R)-2-(diisopropylamino)-1,2-diphenyl ethan-1-ol;
the cupric salt is cupric acetate monohydrate or cupric trifluoromethanesulfonate; and
the condensation reaction is performed at −15-15° C. for 48-120 h.

2. The method of claim 1 , wherein a molar ratio of the compound of formula (II) to the compound of formula (III) to the cupric salt to the chiral (1S,2R)-amino alcohol ligand is 1:1.1-8:0.05-0.15:0.08-0.2.

3. The method of claim 2 , wherein a molar ratio of the compound of formula (II) to the compound of formula (III) to the cupric salt to the chiral (1S,2R)-amino alcohol ligand is 1: 2-6:0.05-0.15:0.08-0.2.

4. The method of claim 1 , wherein the organic solvent is a polar aprotic solvent.

5. The method of claim 2 , wherein the organic solvent is a polar aprotic solvent.

6. The method of claim 3 , wherein the organic solvent is a polar aprotic solvent.

7. The method of claim 4 , wherein the polar aprotic solvent is selected from the group consisting of toluene, carbon tetrachloride, diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform and ethyl acetate.

8. The method of claim 5 , wherein the polar aprotic solvent is selected from the group consisting of toluene, carbon tetrachloride, diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform and ethyl acetate.

9. The method of claim 6 , wherein the polar aprotic solvent is selected from the group consisting of toluene, carbon tetrachloride, diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform and ethyl acetate.

Assignees

• Univ Sichuan

Inventors

• Chen Fener
• Dong Lin
• Xia Yingqi
• Tang Pei
• Xiao Youcai

Classifications

• C07C201/12 Primary

  by reactions not involving the formation of nitro groups · CPC title

• B01J31/184

  mixed aromatic/aliphatic ring systems, e.g. indoline · CPC title

• B01J31/2243

  At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand · CPC title

• B01J2531/16

  Copper · CPC title

• C07B2200/07

  Optical isomers · CPC title