Diethyl Ether → tert-Butyl 4-hydroxy-4-(4-methoxy-2-methylphenyl)piperidine-1-carboxylate

Reaction equation

[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([Mg]Br)=[CH:19][C:18]=1C.[CH2:26](OCC)C>>[OH:1][C:2]1([C:20]2[CH:19]=[CH:18][C:17]([O:16][CH3:15])=[CH:22][C:21]=2[CH3:26])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

Reactant 3

HCID 3283Diethyl Ether

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

HCID 178491913HCID 178491913, compound

Product 1

HCID 118207352tert-Butyl 4-hydroxy-4-(4-methoxy-2-methylphenyl)piperidine-1-carboxylateYield 71%

Procedure

A solution of tert-butyl 4-oxopiperidine-1-carboxylate (2 g, 10 mmol) in diethyl ether (100 mL) was chilled to 0° C., and a solution of (4-methoxy-3-methylphenyl)magnesium bromide (0.5 M in ether) (20 mL, 10 mmol) was added. The reaction mixture was allowed to warm to rt and stirred for 12 h. The reaction mixture was then quenched with a saturated NH4Cl solution and the mixture was diluted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4, and then evaporated under reduced pressure to provide the desired product (2.3 g, 71%); 1H NMR (400 MHz, DMSO-d6) δ 7.27 (d, J=8.0 Hz, 1H), 6.75-6.61 (m, 2H), 4.83 (s, 1H), 3.85-3.77 (m, 2H), 3.71 (s, 3H), 3.17 (d, J=5.0 Hz, 2H), 2.51 (s, 3H), 1.82-1.73 (m, 4H), 1.41 (s, 9H).