2,2,6,6-Tetramethylpiperidine → 1-(3-Bromo-2-fluoro-phenyl)-4-dimethylamino-cyclohexanol

反応式

[Li]CCCC.CC1(C)CCCC(C)(C)N1.[Br:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23].[CH3:24][N:25]([CH3:33])[CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1>>[Br:16][C:17]1[C:18]([F:23])=[C:19]([C:29]2([OH:32])[CH2:30][CH2:31][CH:26]([N:25]([CH3:33])[CH3:24])[CH2:27][CH2:28]2)[CH:20]=[CH:21][CH:22]=1

参加物

反応物 4

HCID 130352,2,6,6-Tetramethylpiperidine

HCID 612591-Bromo-2-fluorobenzene

HCID 103745454-(Dimethylamino)cyclohexan-1-one

HCID 178418339Butyllithium

生成物 1

HCID 588523751-(3-Bromo-2-fluoro-phenyl)-4-dimethylamino-cyclohexanol

実験手順

Add n-BuLi (20.2 mL, 1.6M in hexanes, 32.3 mmol) into a solution of 2,2,6,6-tetramethyl-piperidine (4.56 g, 32.6 mmol) in hexanes (30 mL) at −78° C. Add 1-bromo-2-fluoro-benzene (4.71 g, 26.9 mmol) and stir for 1 hr. Slowly add 4-dimethylamino-cyclohexanone (3.80 mL) in hexanes (30 mL) and stir for 1 hr. Remove the cooling bath and stir for two more hours. Partition the reaction mixture between saturated aqueous NaCl and ethyl acetate, dry the organic phase with anhydrous sodium sulfate, evaporate the solvent, and purify the residue by chromatography on a silica gel column (DCM: 2M NH3 in MeOH, gradient) to give the title compound (2.04 g): MS (ES): m/z=318 (M+H)+ and 316 (M−H)−. 1HNMR (CDCl3): δ 7.43 (m, 2H), 6.98 (m, 1H), 2.45 (m, 2H), 2.21 (s, 6H), 2.13 (m, 1H), 1.92 (m, 2H), 1.64 (m, 4H).