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

HRID 1788280Notes

Reaction equation

HRID 1788280 reaction equation
[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]

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 4311764Sodium borohydrideHCID 86596808HCID 86596808, compound

Product 1

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

Procedure

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).

Workup

  1. customquenched by the addition of aqueous HCl (20 mL) to pH ˜3
  2. customThe solvent was removed by rotary evaporation
  3. extractionthe resulting aqueous mixture was extracted with three 50 mL portions of ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried over Na2SO4
  6. filtrationFiltration and concentration
  7. customby rotary evaporation
  8. customgave the crude product which
  9. customwas purified by flash column chromatography
  10. washeluting with a gradient of 5-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5eb68b1997cb44899342858bcb169ea0
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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