Methyl iodide → 4-(4-Bromophenyl)-4-methoxypiperidine-1-carboxylic acid tert-butyl ester
Reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=2)([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:24]I>C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:11][CH2:12][C:13]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=2)([O:16][CH3:24])[CH2:14][CH2:15]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]Participants
Procedure
Sodium hydride (76 mg, 1.90 mmol) was added portionwise to a solution of 4-(4-bromophenyl)-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (519 mg, 1.46 mmol) in anhydrous THF (10 mL) at 0° C. After 1 h, methyl iodide (136 μL, 2.19 mmol) was added and the reaction mixture was allowed to warm to ambient temperature and stirred for 18 h. The reaction was quenched by the addition of water (10 mL), the organic layer was separated and the aqueous layer back-extracted with DCM (3×10 mL). The combined organic phase was concentrated in vacuo to afford the title compound (607 mg, quantitative). 1H NMR (CDCl3, 400 MHz): 7.49 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 3.97 (d, J=13.0 Hz, 2H), 3.15 (t, J=13.0 Hz, 2H), 2.97 (s, 3H), 1.97 (d, J=13.5 Hz, 2H), 1.83-1.74 (m, 2H), 1.47 (s, 9H). LCMS (Method B): RT=4.61 min.
Workup
- customThe reaction was quenched by the addition of water (10 mL)
- customthe organic layer was separated
- extractionthe aqueous layer back-extracted with DCM (3×10 mL)
- concentrationThe combined organic phase was concentrated in vacuo
Sources & evidence
- ORD record
- ord-d1a95777af034e93a71f3ee2cb9ce72c
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08501765B2
Reaction notes
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