Method for preparing chiral gamma-secondary amino alcohol

Patent metadata

Field	Value
Publication number	US-10370323-B2
Application number	US-201515514243-A
Country	US
Kind code	B2
Filing date	Sep 23, 2015
Priority date	Sep 26, 2014
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

A method for preparing chiral γ-secondary amino alcohol includes: adding into a solvent an acid addition salt of β-secondary amino ketone represented by general formula (1), an alkali, a metal salt additive and a diphosphine-rhodium complex, so as to carry out a reaction in a hydrogen atmosphere and obtain a chiral γ-secondary amino alcohol compound represented by general formula (2). In general formula (2), Ar represents an aryl group with or without substituent group(s), R represents an alkyl group or an aralkyl group, and HY represents an acid. The synthesis scheme has a simple process, the metal salt additive remarkably improves the effect of a rhodium-catalyzed asymmetric hydrogenation technology, and accordingly, the reaction yield and the optical purity of a product are improved, the production process is simplified, production costs are reduced, and the synthesis scheme is highly suitable for mass industrial production.

First claim

The invention claimed is:

1. A method for preparing a chiral γ-secondary amino alcohol, comprising the steps of:
adding into a solvent an acid addition salt of β-secondary amino ketone represented by the general formula (1), an alkali, a metal salt additive and a diphosphine-rhodium complex to react in hydrogen atmosphere, so as to obtain a chiral compound of γ-secondary amino alcohol represented by the general formula (2),

in the general formulas (1) and (2), Ar represents an aryl group with or without substituent group(s), R represents an alkyl group or an aralkyl group, and HY represents an acid; and
wherein:
the diphosphine-rhodium complex is [Rh(L)(L′)]X, wherein
L is any one chiral diphosphine ligand selected from the group consisting of (R,R)-QuinoxP*, (R,R)-BenzP*, (R,R)-Miniphos, (S,S)-Bi sP*, (S,S)-QuinoxP*, (S,S)-BenzP*, (S,S)-Miniphos and (R,R)-BisP* shown as follows,

L′ is any one auxiliary diene ligand selected from the group consisting of 1,5-cyclooctadiene and 2,5-norbornadiene,
X is any one anion selected from the group consisting of SbF 6 − and BF 4 − .

2. The method for preparing a chiral γ-secondary amino alcohol according to claim 1 , wherein:
in the general formulas (1) and (2),
Ar is any one selected from the group consisting of phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3 -chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3 -bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 1-naphthyl, 2-naphthyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-furyl, 2-thienyl, 3,4-dimethoxyphenyl, 3,4-dimethylphenyl, 3,4-dichlorophenyl and 3,4-methylenedioxyphenyl;
R is any one selected from the group consisting of methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, tert-butyl, pentyl, iso-pentyl, neo-pentyl, hexyl, heptyl, octyl and benzyl.

3. The method for preparing a chiral γ-secondary amino alcohol according to claim 1 , wherein:
in the general formula (1), HY is any one selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, tartaric acid, p-methylbenzenesulfonic acid, trifluoromethanesulfonic acid, salicylic acid, tetrafluoroboric acid, hexafluorophosphoric acid and hexafluoroantimonic acid.

4. The method for preparing a chiral γ-secondary amino alcohol according to claim 1 , wherein:
the molar ratio of the diphosphine-rhodium complex to the acid addition salt of β-secondary amino ketone represented by the general formula (1) is 1/200˜1/20000.

5. A method for preparing a chiral γ-secondary amino alcohol, comprising the steps of:
adding into a solvent an acid addition salt of β-secondary amino ketone represented by the general formula (1), an alkali, a metal salt additive and a diphosphine-rhodium complex to react in hydrogen atmosphere, so as to obtain a chiral compound of γ-secondary amino alcohol represented by the general formula (2),

in the general formulas (1) and (2), Ar represents an aryl group with or without substituent group(s), R represents an alkyl group or an aralkyl group, and HY represents an acid; and
the metal salt additive is any one selected from the group consisting of zinc acetate, cerium chloride, zinc trifluoromethane sulfonate, copper chloride, copper acetate, zinc iodide, copper iodide, zinc chloride, magnesium sulfate, ferric chloride and aluminum chloride.

6. The method for preparing a chiral γ-secondary amino alcohol according to claim 1 , wherein:
the alkali is any one selected from the group consisting of potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium phosphate, dipotassium phosphate, monopotassium phosphate, triethylamine, sodium acetate and potassium tert-butoxide.

7. The method for preparing a chiral γ-secondary amino alcohol according to claim 1 , wherein:
the solvent is a polar solvent.

8. The method for preparing a chiral γ-secondary amino alcohol according to claim 7 , wherein:
the solvent is any one or two or more selected from the group consisting of ethyl acetate, methylene chloride, tetrahydrofuran, methanol, ethanol, isopropanol and trifluoroethanol.

9. The method for preparing a chiral γ-secondary amino alcohol according to claim 1 , wherein:
the pressure of hydrogen is 10˜100 bar in the hydrogen atmosphere, the reaction temperature is −20˜100° C., and the reaction time is 1˜48 hours.

10. The method for preparing a chiral γ-secondary amino alcohol according to claim 2 , wherein:
the molar ratio of the diphosphine-rhodium complex to the acid addition salt of β-secondary amino ketone represented by the general formula (1) is 1/200˜1/20000.

11. The method for preparing a chiral γ-secondary amino alcohol according to claim 2 , wherein:
the metal salt additive is any one selected from the group consisting of zinc acetate, cerium chloride, zinc trifluoromethane sulfonate, copper chloride, copper acetate, zinc iodide, copper iodide, zinc chloride, magnesium sulfate, ferric chloride and aluminum chloride.

12. The method for preparing a chiral γ-secondary amino alcohol according to claim 2 , wherein:
the alkali is any one selected from the group consisting of potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium phosphate, dipotassium phosphate, monopotassium phosphate, triethylamine, sodium acetate and potassium tert-butoxide.

13. The method for preparing a chiral γ-secondary amino alcohol according to claim 2 , wherein:
the solvent is a polar solvent.

14. The method for preparing a chiral γ-secondary amino alcohol according to claim 2 , wherein:
the pressure of hydrogen is 10˜100 bar in the hydrogen atmosphere, the reaction temperature is −20˜100° C., and the reaction time is 1˜48 hours.

Assignees

• Univ Shanghai Jiaotong
• Nippon Chemical Ind

Inventors

• Zhang Wanbin
• Zhang Zhenfeng
• Hu Qiupeng

Classifications

• C07D333/20

  by nitrogen atoms (nitro, nitroso radicals C07D333/12) · CPC title

• C07D333/16

  by oxygen atoms · CPC title

• C07D307/42

  Singly bound oxygen atoms · CPC title

• C07C213/00 Primary

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title

• C07B53/00

  Asymmetric syntheses · CPC title