Water → tert-Butyl 4-(4-(trifluoromethyl)phenoxy)piperidine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].F[C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1.O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A stirred solution of 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (134.8 g) in N,N-dimethylformamide (850 m) was cooled in an ice bath under a nitrogen atmosphere. Potassium tert butoxide (75.2 g) was added in portions such that the temperature did not exceed 22° C. and the resulting mixture was maintained at 0° C. for a further 1.5 hours when 4-fluorobenzotrifluoride (100 g) was added dropwise over 15 minutes. The reaction mixture was allowed to warm to room temperature and stirred overnight. Water (200 ml) was added and the mixture was extracted with tert butyl methyl ether (1×400 ml, 1×300 ml, 1×200 ml). The combined organic extracts were washed with water (2×400 ml), brine (200 ml) and then dried over magnesium sulphate and evaporated in vacuo to leave the title compound as an off-white/pale yellow solid (206.4 g)
Workup
- customdid not exceed 22° C.
- additionwas added dropwise over 15 minutes
- extractionthe mixture was extracted with tert butyl methyl ether (1×400 ml, 1×300 ml, 1×200 ml)
- washThe combined organic extracts were washed with water (2×400 ml), brine (200 ml)
- dry with materialdried over magnesium sulphate
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-5f022a7b73ef434cbc274475ab152744
- Source dataset
- uspto-grants-2006_03
- Patent number
- US07015234B2
Reaction notes
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