Ethyl Acetate → (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[(4-bromophenyl)hydroxymethyl]pyrrolidine

HRID 725949Notes

Reaction equation

HRID 725949 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:22][C@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:20][C@H:17]1[CH:18]=[O:19])=[O:15])([CH3:12])([CH3:11])[CH3:10].[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1.O>[C:9]([O:13][C:14]([N:16]1[CH2:22][C@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:20][C@H:17]1[CH:18]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[OH:19])=[O:15])([CH3:12])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 115221-Bromo-4-iodobenzeneHCID 25517Ammonium ChlorideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

Product 1

HCID 22881065(2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[(4-bromophenyl)hydroxymethyl]pyrrolidineYield 85.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 4-bromo-1-iodobenzene (9.44 g, 33.4 mmol) in tetrahydrofuran (10 ml) was added dropwise to a solution of 1.6M n-butyl lithium-hexane solution (19.0 ml, 30.3 mmol) in tetrahydrofuran (50 ml) at -78° C. for in a nitrogen stream over 15 minutes. This reaction solution was stirred -78° C. for 40 minutes and then a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (5.0 g, 15.2 mmol) in tetrahydrofuran (17 ml) was added dropwise thereto over 10 minutes. The reaction solution was stirred at -78° C. for 1.5 hours and then saturated ammonium chloride solution was added thereto. The reaction solution was poured into a liquid mixture of ethyl acetate with water. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off in vacuo and the resulting oily residue was subjected to silica gel column chromatography (Wakogel™ C-300, 200 ml; ethyl acetate-heptane 2:3→3:2) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[(4-bromophenyl)hydroxymethyl]pyrrolidine (6.30 g, yield: 85.3%) as a pale yellow oily substance.

Workup

  1. waitover 10 minutes
  2. stirringThe reaction solution was stirred at -78° C. for 1.5 hours
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off in vacuo

Sources & evidence

ORD record
ord-5d5ed10171b045efa649eff89d3e0e6d
Source dataset
uspto-grants-1998_01
Patent number
US05707987

Reaction notes

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