4-(Trifluoromethyl)aniline → methyl (3R)-3-(4-trifluoromethylphenylamino)-pentanoate

HRID 1865311Notes

Reaction equation

O=[C:2]([CH2:8][CH3:9])[CH2:3][C:4]([O:6][CH3:7])=[O:5].[F:10][C:11]([F:20])([F:19])[C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1>CC(O)C>[F:10][C:11]([F:19])([F:20])[C:12]1[CH:13]=[CH:14][C:15]([NH:16][C@H:2]([CH2:8][CH3:9])[CH2:3][C:4]([O:6][CH3:7])=[O:5])=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

[RuCl(p-cymene)((R)-segphos)]Cl(17.6 mg, 0.0192 mmol), methyl 3-oxopentanoate (500 mg, 3.842 mmol), 4-trifluoromethylaniline (619 mg, 3.842 mmol) and 2-propanol (2.5 mL) were placed in a 2.5 mL-stainless autoclave under atmosphere of nitrogen, and the mixture was stirred under a hydrogen pressure of 3 MPa at 80° C. for 15 hours. After completion of the reaction, the solvent was removed by evaporation in vacuo, and the residue was purified by column chromatography on silica gel (eluent: hexane ethyl acetate=3/1) to give methyl (3R)-3-(4-trifluoromethylphenylamino)-pentanoate (109 mg) as a colorless oil in 10.3% yield. The enantiomeric excess of the product was found to be 92.7% ee determined by HPLC analysis using a SUMICHIRAL OA-2500 column (available from SUMIKA CHEMICAL ANALYSIS SERVICE LTD.).

Workup

customAfter completion of the reaction
customthe solvent was removed by evaporation in vacuo
customthe residue was purified by column chromatography on silica gel (eluent: hexane ethyl acetate=3/1)

Sources & evidence

ORD record: ord-131e95a1010e4389a754b5e00d6619e6
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07626034B2

Reaction notes

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