4-Fluorobenzaldehyde → cis-2-(4-Fluoro-benzylamino)-cycloheptanecarboxylic acid methyl ester
Reaction equation
Cl.[CH3:2][O:3][C:4]([C@@H:6]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][C@@H:7]1[NH2:13])=[O:5].C([O-])(=O)C.[Na+].[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][C@@H:7]1[NH:13][CH2:24][C:23]1[CH:26]=[CH:27][C:20]([F:19])=[CH:21][CH:22]=1)=[O:5]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 25 °C
Procedure
cis-2-Amino-cycloheptanecarboxylic acid methyl ester hydrochloride (0.8 g, 3.86 mmol) was suspended in methanol (20 mL). Sodium acetate (0.63 g, 7.7 mmol) was added followed by 4 Å powdered molecular sieves (0.8 g) followed by 4-fluoro-benzaldehyde (0.48 g, 3.86 mmol). Sodium cyanoborohydride (0.48 g, 7.7 mmol) was added and the mixture stirred at 25° C. for 16 h. The mixture was poured into a 1:1 mixture of saturated aqueous sodium bicarbonate solution (200 mL) and ethyl acetate (200 mL). After shaking, both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous brine solution (50 mL), dried over magnesium sulfate and concentrated in vacuo to afford the crude product, cis-2-(4-fluoro-benzylamino)-cycloheptanecarboxylic acid methyl ester (0.56 g, 2 mmol, 52%), as a clear oil. LC-MS (ESI) calcd for C16H22FNO2 279.16, found 280.3 [M+H+].
Workup
- stirringAfter shaking
- washThe organic layer was further washed with saturated aqueous brine solution (50 mL)
- dry with materialdried over magnesium sulfate
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-a68860372c174cc8aafdf6fef6d3c5de
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07582626B2
Reaction notes
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