4-(Trifluoromethyl)benzaldehyde → (1R,2S)-2-(4-trifluoromethyl-benzylamino)-cyclopentanecarboxylic acid methyl ester
Reaction equation
Cl.[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[NH2:11])=[O:5].[F:12][C:13]([F:23])([F:22])[C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C.C(O)(=O)C>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[NH:11][CH2:18][C:17]1[CH:16]=[CH:15][C:14]([C:13]([F:12])([F:22])[F:23])=[CH:21][CH:20]=1)=[O:5]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 25 °C
Procedure
(1R,2S)-2-Amino-cyclopentanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 11a, 130 mg, 0.91 mmol) was dissolved in methanol (5 mL). 4-Trifluoromethyl-benzaldehyde (160 mg, 0.91 mmol) was added, stirred at 25° C. for 15 min, then acetic acid (0.2 mL) was added, followed by sodium cyanoborohydride (150 mg, 2.3 mmol) and the mixture was stirred at 25° C. for 16 h. The mixture was poured into a mixture of saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (200 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution (100 mL), saturated aqueous brine solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product (1R,2S)-2-(4-trifluoromethyl-benzylamino)-cyclopentanecarboxylic acid methyl ester (200 mg, 0.664 mmol, 73%) as a clear oil. LC-MS (ESI) calcd for C15H18F3NO2 301.13, found 302.2 [M+H+].
Workup
- stirringthe mixture was stirred at 25° C. for 16 h
- washThe organic layer was washed with saturated aqueous sodium bicarbonate solution (100 mL), saturated aqueous brine solution (100 mL)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-7da7db89d704472bb07ec2df5eb3f4e5
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07582626B2
Reaction notes
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