tert-Butyl(4-chlorobutoxy)dimethylsilane → HCID 59201333, compound

HRID 451668Notes

Reaction equation

HRID 451668 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1)=[O:6].[C:23]([Si:27]([O:30][CH2:31][CH2:32][CH2:33][CH2:34]Cl)([CH3:29])[CH3:28])([CH3:26])([CH3:25])[CH3:24]>C1COCC1>[Si:27]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][C@:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH2:8]1)([C:4]1[CH:20]=[CH:21][CH:22]=[C:2]([Cl:1])[CH:3]=1)[OH:6])([C:23]([CH3:24])([CH3:25])[CH3:26])([CH3:28])[CH3:29]

Participants

4

Reactant 2

HCID 3382519tert-Butyl(4-chlorobutoxy)dimethylsilaneHCID 46831638(R)-Tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate

Product 1

HCID 59201333HCID 59201333, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)-tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate (1.62 g, 5 mmol) in anhydrous THF (20 mL) under N2 was cooled in a dry ice-acetone bath. The Grignard reagent derived from tert-butyl-(4-chloro-butoxy)-dimethyl-silane (50 mL) prepared above was added dropwise. After addition, the mixture was allowed to warm to rt and stirred for 2 h (monitored by tlc). The reaction was quenched with satd aq NH4Cl (70 mL) and extracted with EtOAc (3×40 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 10:90 EtOAc/hexane to afford (R)-tert-butyl 3-((S)-5-(tert-butyldimethylsilyloxy)-1-(3-chlorophenyl)-1-hydroxypentyl)piperidine-1-carboxylate (1.65 g, 65%). 1H NMR (400 MHz, CDCl3): 0.02 (s, 6H), 7.30 (d, 2H), 0.85 (s, 9H), 1.47 (s, 9H), 1.92 (m, 3H), 2.52 (m, 3H), 3.56 (m, 2H), 3.63 (m, 2H), 3.97-4.21 (m, 2H), 4.36 (m, 1H), 7.16-7.25 (m, 3H), 7.36 (m, 1H). MS (E/Z): 512 (M+H+)

Workup

  1. customprepared
  2. additionabove was added dropwise
  3. additionAfter addition
  4. customThe reaction was quenched with satd aq NH4Cl (70 mL)
  5. extractionextracted with EtOAc (3×40 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel eluting with 10:90 EtOAc/hexane

Sources & evidence

ORD record
ord-bb363c45821b4d1fafc16980a753180d
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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