Tetrahydrofuran → 2-trimethylsilylethyl (3RS,4RS)-4-(3-bromophenyl)-3-(2-trimethylsilyl-ethoxycarbonyloxy)-piperidine-1-carboxylate

HRID 1004928Notes

Reaction equation

HRID 1004928 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=2)[CH:10](O)[CH2:9]1)C1C=CC=CC=1.[C:22](=[O:25])([O-:24])[O-:23].[Li+].[Li+].Cl[C:29]([O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])=[O:30].O1[CH2:42][CH2:41]CC1>C1(C)C=CC=CC=1>[Br:20][C:16]1[CH:15]=[C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:29]([O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])=[O:30])[CH2:13][CH:12]2[O:25][C:22]([O:24][CH2:41][CH2:42][Si:34]([CH3:36])([CH3:35])[CH3:33])=[O:23])[CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11125Lithium CarbonateHCID 109101682-(Trimethylsilyl)ethyl chloroformateHCID 22127354(3RS,4RS)-1-benzyl-4-(3-bromophenyl)-piperidin-3-ol

Product 1

HCID 539146402-trimethylsilylethyl (3RS,4RS)-4-(3-bromophenyl)-3-(2-trimethylsilyl-ethoxycarbonyloxy)-piperidine-1-carboxylateYield 43%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-50 °C

Procedure

A solution of 691 mg (2.00 mmol) of (3RS,4RS)-1-benzyl-4-(3-bromophenyl)-piperidin-3-ol in 3 ml of absolute tetrahydrofuran was treated with 163 mg (2.20 mmol) of lithium carbonate and cooled to -50° C. A solution of 722 mg (4.00 mmol) of β-trimethylsilylethyl chloroformate [Synthesis 346 (1987)] in 4 ml of toluene was added dropwise thereto at -50° C. The reaction mixture was warmed to room temperature and stirred for 24 hours. Subsequently, the mixture was partitioned between methylene chloride and water, the organic phase was dried over magnesium sulphate and finally the solvent was removed under reduced pressure. The crude product (0.8 g) was purified by chromatography on silica gel with methylene chloride as the eluent. There were obtained 470 mg (43% of theory) of 2-trimethylsilylethyl (3RS,4RS)-4-(3-bromophenyl)-3-(2-trimethylsilylethoxycarbonyloxy)-piperidine-1-carboxylate as a light yellow oil, which was used directly in the next step.

Workup

  1. customat -50° C
  2. temperatureThe reaction mixture was warmed to room temperature
  3. customSubsequently, the mixture was partitioned between methylene chloride and water
  4. dry with materialthe organic phase was dried over magnesium sulphate
  5. customfinally the solvent was removed under reduced pressure
  6. customThe crude product (0.8 g) was purified by chromatography on silica gel with methylene chloride as the eluent

Sources & evidence

ORD record
ord-639babbb1ef742d69741c7efc3835537
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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