Triethylamine → 2-(3,5-Difluoro-4-(trifluoromethyl)phenyl)-1-(methoxy-carbonyl)piperidine-4-carboxylic acid
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]2[CH2:18][CH:17]([C:19]([O:21]C)=[O:20])[CH2:16][CH2:15][N:14]2[C:23]([O:25][CH3:26])=[O:24])[CH:5]=[C:6]([F:12])[C:7]=1[C:8]([F:11])([F:10])[F:9].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:12][C:6]1[CH:5]=[C:4]([CH:13]2[CH2:18][CH:17]([C:19]([OH:21])=[O:20])[CH2:16][CH2:15][N:14]2[C:23]([O:25][CH3:26])=[O:24])[CH:3]=[C:2]([F:1])[C:7]=1[C:8]([F:9])([F:11])[F:10]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
Dimethyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate (2.851 g, 7.48 mmol) was dissolved in acetonitrile (25 mL) and water (2.5 mL), then lithium bromide (5.19 g, 59.82 mmol) was added followed by triethylamine (4.15 mL, 29.91 mmol). The reaction mixture was heated under reflux for 1 h. MTBE (150 mL) and water (150 mL) were added, shaken and the phases separated. The organic phase was extracted with water (2×150 mL). The combined aqueous phases were acidified with 3 M HCl to pH 1 and extracted with MTBE (2×450 mL). The combined organic phases were dried over Na2SO4, filtered and evaporated in vacuo yielding 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-1-(methoxy-carbonyl)piperidine-4-carboxylic acid (2.363 g, 86%). MS m/z 368 (M+H)+
Workup
- temperatureThe reaction mixture was heated
- temperatureunder reflux for 1 h
- customthe phases separated
- extractionThe organic phase was extracted with water (2×150 mL)
- extractionextracted with MTBE (2×450 mL)
- dry with materialThe combined organic phases were dried over Na2SO4
- filtrationfiltered
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-592d55a8015b4d2ca3e491fa99408042
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
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