Diethyl Ether → 4-Acetyl-piperidine-1-carboxylic acid tert-butyl ester
Reaction equation
CON(C)[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5].[CH3:20]COCC>>[C:4]([CH:6]1[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:10][CH2:11]1)(=[O:5])[CH3:20]Participants
Conditions
- Temperature
- 0 °C
Procedure
A 3-neck, 250 mL round bottom flask was charged with a solution of tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (9.9 g) in Et2O (120 mL). The flask was purged with nitrogen and then cooled in a CO2/acetone bath. Methylmagnesium bromide (26.8 mL of a 3.0 M solution in Et2O, 80 mmol) was added dropwise over 10 min to the amide. The resulting thick mixture was warmed to 0° C. and then stirred for 40 min before being poured into 2 M HCl solution (50 mL). The mixture was diluted with Et2O (100 mL), washed with brine, dried (MgSO4) and concentrated on a rotary evaporator to give tert-butyl 4-acetylpiperidine-1-carboxylate (7.3 g, 32.1 mmol, 80% yield) as a colorless oil. The product partly crystallized on standing at RT. 1H-NMR (400 MHz, CDCl3) δ ppm 4.06 (2 H, s), 2.74 (2 H, s), 2.42 (1 H, s), 2.12 (2 H, s), 1.78 (2 H, s), 1.49 (2 H, s), 1.41 (9 H, s).
Workup
- customThe flask was purged with nitrogen
- temperaturecooled in a CO2/acetone bath
- additionMethylmagnesium bromide (26.8 mL of a 3.0 M solution in Et2O, 80 mmol) was added dropwise over 10 min to the amide
- additionbefore being poured into 2 M HCl solution (50 mL)
- additionThe mixture was diluted with Et2O (100 mL)
- washwashed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated on a rotary evaporator
Sources & evidence
- ORD record
- ord-18b0d890a4e849d59f8a16f37db308be
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354432B2
Reaction notes
Loading…