Ammonium Chloride → (2S,3R)-1-tert-Butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine

HRID 2287972Notes

Reaction equation

HRID 2287972 reaction equation
Cl[Mg][CH2:3][C:4]([CH2:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[CH2:5].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[C@@H:22]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>C1COCC1>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH2:24][C@@:23]([OH:27])([CH2:3][C:4](=[CH2:5])[CH2:6][O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@@H:22]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 10956740(2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-oneHCID 178458313HCID 178458313, compound

Product 1

HCID 57220489(2S,3R)-1-tert-Butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-(chloromagnesio)-2-(phenoxymethyl)-1-propene in THF (0.91M, 3 ml) (Louw et. al., Tetrahedron, 48, 6087-6104, 1992, prepared from 2.74 mmol of 3-chloro-2-(phenoxymethyl)-1-propene) was slowly added to a solution of (2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-one (Preparation 1) in THF (3 ml). The mixture was stirred at room temperature for 1 hours, then saturated aqueous ammonium chloride (20 ml) was added and the mixture was extracted with ethyl acetate (20 ml). The organic phase was washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/ethyl acetate (100:0 increasing to 80:20) to give the title compound. 1H NMR (360 MHz, CDCl3) δ 7.48 (2H, d, J=6.9 Hz), 7.35-7.2 (6H, m), 6.9-6.88 (3H, m), 5.4 (1H, s), 5.15 (2H, d, J=13.7 Hz), 4.61 (2H, s), 4.11 (2H, m), 3.17 (1H, m), 2.66 and 2.59 (2H, AB d, J=14.0 Hz), 1.95 (2H, m), 1.79 (2H, m), and 1.36 (9H, s). m/z (ES+) 424 (M+1).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 ml)
  2. washThe organic phase was washed with brine
  3. dry with materialdried (MgSO4)
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with hexane/ethyl acetate (100:0 increasing to 80:20)

Sources & evidence

ORD record
ord-88678fcddd984b66822fef17ff74826a
Source dataset
uspto-grants-2000_07
Patent number
US06087348

Reaction notes

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