Hexane → Ethyl N-Boc-4-fluoropiperidine-4-carboxylate
Reaction equation
[N:1]1([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:37])(=O)=O)=CC=1.CCCCCC>C1COCC1>[F:37][C:4]1([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2][N:1]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:6][CH2:5]1Participants
Procedure
A solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (1.50 g, 5.81 mmol) in THF (25.0 mL) was cooled to −78° C. followed by drop wise addition of LDA (1.80 M in THF, 6.50 mL, 11.62 mmol) and the mixture stirred at the same temperature for 45 min followed by addition of N-fluorobenzenesulphonimide (3.60 g, 11.62 mmol) at −78° C. The temperature of the reaction was slowly raised to rt and left to stir for 5-6 h. The reaction was then cooled to 0° C. and quenched by drop wise addition of saturated NH4Cl solution (50 mL), extracted with EtOAc (3×100 mL) and the combined organics was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 2% EtOAc:hexane to obtain the product as an orange viscous liquid (1.0 g, 63% yield). MS: 276.27 [M+H]+.
Workup
- waitleft
- stirringto stir for 5-6 h
- temperatureThe reaction was then cooled to 0° C.
- customquenched by drop wise addition of saturated NH4Cl solution (50 mL)
- extractionextracted with EtOAc (3×100 mL)
- washthe combined organics was washed with brine
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe crude residue was purified over 100-200 M silica-gel
Sources & evidence
- ORD record
- ord-8bd86b9401144c41a63dfafa6568cbce
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181234B2
Reaction notes
Loading…