(2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-one → (2S,3R)-1-tert-Butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine

HRID 1003253Notes

Reaction equation

HRID 1003253 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]>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

4

Reactant 2

HCID 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 tetrahydrofuran solution of 3-(chloromagnesio)-2-(phenoxymethyl)-1-propene (0.91 M, 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 (Desc.1) in THF (3 ml). The solution was stirred at room temperature for 1 hour, quenched by addition of saturated ammonium chloride solution (20 ml) and extracted with ethyl acetate (20 ml). The organic phase was washed (saturated brine), dried (MgSO4), evaporated to a small volume and purified by chromatography on silica gel eluting with hexane containing increasing proportions of ethyl acetate between 0% to 20%. Evaporation of the fractions gave (2S,3R)-1-tert-butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine. MS (ES+) m/z 424 (M+H), 324 (M+2H-tBuOCO--), 368 (M+2H-tBu). 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), 1.36 (9H, s).

Workup

  1. customquenched by addition of saturated ammonium chloride solution (20 ml)
  2. extractionextracted with ethyl acetate (20 ml)
  3. washThe organic phase was washed (saturated brine)
  4. dry with materialdried (MgSO4)
  5. customevaporated to a small volume
  6. custompurified by chromatography on silica gel eluting with hexane containing
  7. temperatureincreasing proportions of ethyl acetate between 0% to 20%
  8. customEvaporation of the fractions

Sources & evidence

ORD record
ord-a2f2b2a9df0945fa95b38f63fce31efb
Source dataset
uspto-grants-2000_04
Patent number
US06046195

Reaction notes

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