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

HRID 725948

Reaction equation

HRID 725948 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 p-bromoiodobenzene (9.44 g, 33.4 mmol) in tetrahydrofuran (10 ml) was added dropwise to a solution of 1.6M butyl lithium-hexane solution (19.0 ml, 30.3 mmol) in tetrahydrofuran (50 ml) at -78° C. in a nitrogen stream over 15 minutes. The resulting reaction solution was stirred at -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. After addition of saturated aqueous ammonium chloride, the reaction solution was poured into a liquid mixture of ethyl acetate with water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. 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. customThe resulting reaction solution
  2. waitover 10 minutes
  3. stirringThe reaction solution was stirred at -78° C. for 1.5 hours
  4. washThe organic layer was washed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bcd56eb2d9464ea4901d16bc1507a4a7
Source dataset
uspto-grants-1998_01
Patent number
US05707987

Linked notes

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