Method for manufacturing cyclopropane compound

Patent metadata

Field	Value
Publication number	US-12098137-B2
Application number	US-201917274059-A
Country	US
Kind code	B2
Filing date	Sep 5, 2019
Priority date	Sep 7, 2018
Publication date	Sep 24, 2024
Grant date	Sep 24, 2024

Abstract

The present invention provides an industrially advantageous production method of (1R,2S)-2-{[((2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide.(1R,2S)-2-{[((2,4-Dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (compound [A]) is produced by an industrially advantageous method by a route via a novel compound.wherein each symbol is as described in the description.

First claim

The invention claimed is:

1. A method of selectively producing an optically active compound represented by the formula [2]

wherein R 1 is an alkylcarbonyl group, and R 2 is an alkyl group,
the method comprising:
reacting a compound represented by the formula [1]

wherein R 1 is an alkylcarbonyl group,
with an alkyl diazoacetate in the presence of copper trifluoromethanesulfonate and an optically active compound represented by the formula [5] or formula [6]

wherein t Bu is a tert-butyl group,
in an organic solvent.

2. A method of producing an optically active compound represented by the formula [4]

the method comprising:
selectively producing an optically active compound represented by the formula [2] by the method of claim 1 ,

wherein R 1 is an alkylcarbonyl group, and R 2 is an alkyl group;
subjecting the optically active compound represented by the formula [2] to alkaline hydrolysis to produce an optically active compound represented by the formula [3]

wherein X is an alkali metal; and
subjecting the optically active compound represented by the formula [3] to a cyclization reaction, thereby producing the optically active compound represented by the formula [4].

3. A method of producing an optically active compound represented by the formula [4]

the method comprising:
reacting a compound represented by the formula [1]

wherein R 1 is an alkylcarbonyl group,
with an alkyl diazoacetate in the presence of copper trifluoromethanesulfonate and an optically active compound represented by the formula [5] or formula [6]

wherein t Bu is a tert-butyl group,
in an organic solvent to produce a mixture comprising an optically active compound represented by the formula [2]

wherein R 2 is an alkyl group, and R 1 is an alkylcarbonyl group,
and an optically active compound represented by the formula [2a]

wherein R 1 is an alkylcarbonyl group and R 2 is an alkyl group;
subjecting the mixture comprising the optically active compound represented by the formula [2] and the optically active compound represented by the formula [2a] to alkaline hydrolysis to produce a mixture comprising an optically active compound represented by the formula [3]

wherein X is an alkali metal,
and an optically active compound represented by the formula [3a]

wherein X is an alkali metal;
subjecting the optically active compound represented by the formula [3] to cyclization by adjusting the mixture comprising the optically active compound represented by the formula [3] and the optically active compound represented by the formula [3a] to pH 7.0 or lower with an acid to produce a mixture comprising an optically active compound represented by the formula [4]

and an optically active compound represented by the formula [3b]

and
subjecting the mixture comprising the optically active compound represented by the formula [4] and the optically active compound represented by the formula [3b] to an extraction operation with an aromatic hydrocarbon solvent and a liquid separation operation to remove the optically active compound represented by the formula [3b] from the mixture comprising the optically active compound represented by the formula [4] and the optically active compound represented by the formula [3b].

4. The method according to claim 1 , wherein the reacting of the compound represented by the formula [1] with the alkyl diazoacetate is carried out in the presence of copper trifluoromethanesulfonate and an optically active compound represented by the formula [5].

5. The method according to claim 3 , further comprising washing the mixture comprising the optically active compound represented by the formula [3] and the optically active compound represented by the formula [3a] with an aromatic hydrocarbon solvent, and then removing the organic layer.

6. The method according to claim 3 , wherein the mixture comprising the optically active compound represented by the formula [4] and the optically active compound represented by the formula [3b] is adjusted to pH 6.0 to 8.0, before the extraction operation with an aromatic hydrocarbon solvent and the liquid separation operation.

Assignees

• Sumitomo Chemical Co

Inventors

• Yamauchi Kazuhiro
• Tomokawa Junichi

Classifications

• C07D307/93

  condensed with a ring other than six-membered · CPC title

• C07D213/75

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07C309/66

  Methanesulfonates · CPC title

• C07C303/26

  of esters of sulfonic acids · CPC title

• C07C67/347

  by addition to unsaturated carbon-to-carbon bonds · CPC title