Acetic Acid → 4-(4-Chloro-3-trifluoromethylsulfanyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[S:9][C:10]([F:13])([F:12])[F:11].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C.ClCCl>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([S:9][C:10]([F:11])([F:12])[F:13])[CH:4]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
4-Chloro-3-trifluoromethylsulfanyl-phenylamine (683 mg; 3.00 mmol), 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (598 mg; 3.00 mmol) and sodium triacetoxyborohydride (1.9 g; 9.00 mmol) are suspended in dichloroethane (25 mL) and the resulting mixture is stirred for 1 day. Acetic acid is then added (0.18 mL) and the reaction mixture is stirred for additional 9 days. The suspension is then diluted with dichloromethane (10 mL) and is washed with water (20 mL). The organic phase is then washed with aq. sat. sodium carbonate (10 mL), water (10 mL) and is then dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification of the crude by column chromatography on silica gel (dichloromethane) affords the desired product (580 mg; 1.41 mmol).
Workup
- stirringthe reaction mixture is stirred for additional 9 days
- washis washed with water (20 mL)
- washThe organic phase is then washed with aq. sat. sodium carbonate (10 mL), water (10 mL)
- dry with materialis then dried over magnesium sulphate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customPurification of the crude by column chromatography on silica gel (dichloromethane)
Sources & evidence
- ORD record
- ord-7b0eed05c08e497fb5582d7c36f39f4f
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096524B2
Reaction notes
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