Isopropanol → 4-(4-Bromo-phenyl)-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester

反応式

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=2)(CC=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].[CH:26]([OH:29])(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:18]=[CH:19][C:20]([Br:23])=[CH:21][CH:22]=2)([CH2:26][OH:29])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

参加物

反応物 3

HCID 3776Isopropanol

HCID 4311764Sodium borohydride

HCID 86596808HCID 86596808、化合物

生成物 1

HCID 576031994-(4-Bromo-phenyl)-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester

実験手順

To a solution of 1.78 g of 4-(4-bromo-phenyl)-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester from Step 3 (4.85 mmol, 1 eq) in 25 mL of isopropanol was added NaBH4 (0.201 g, 5.33 mmol, 1.1 eq). The mixture was stirred at room temperature for 20 h and then quenched by the addition of aqueous HCl (20 mL) to pH ˜3. The solvent was removed by rotary evaporation and the resulting aqueous mixture was extracted with three 50 mL portions of ethyl acetate. The organic extracts were combined and washed with saturated brine and dried over Na2SO4. Filtration and concentration by rotary evaporation gave the crude product which was purified by flash column chromatography eluting with a gradient of 5-20% ethyl acetate in hexane to give 1.36 g of the title compound 4-(4-bromo-phenyl)-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester 49 as a pale foam. 1H NMR (300 MHz, CDCl3): δ 7.38-7.18 (m, 4H), 4.35-4.19 (br. d, 2H), 2.83-2.76 (t, 2H), 2.70-2.58 (m, 1H), 1.86-1.78 (d, 2H), 1.70-1.58 (m, 3H), 1.50 (s, 9H).