Ethyl Acetate → (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[alpha-hydroxy-4-(methoxymethoxymethyl)benzyl]pyrrolidine

HRID 725954Notes

Reaction equation

HRID 725954 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][O:11][CH3:12])=[CH:4][CH:3]=1.[C:13]([O:17][C:18]([N:20]1[CH2:26][C@H:25]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:24][C@H:21]1[CH:22]=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1.O>[C:13]([O:17][C:18]([N:20]1[CH2:26][C@H:25]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:24][C@H:21]1[CH:22]([OH:23])[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][O:11][CH3:12])=[CH:4][CH:3]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 110207131-Bromo-4-(methoxymethoxymethyl)benzene

Product 1

HCID 22881080(2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[alpha-hydroxy-4-(methoxymethoxymethyl)benzyl]pyrrolidineYield 59.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1.6M n-Butyl lithium-hexane solution (104 ml, 167 mmol) was added dropwise to a solution of 1-bromo-4-(methoxymethoxymethyl)benzene (38.6 g, 167 mmol) in tetrahydrofuran (350 ml) at -78° C. in a nitrogen stream over 30 minutes. This reaction solution was stirred at -78° C. for 30 minutes and then a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (27.5 g, 83.5 mmol) in tetrahydrofuran (300 ml) was added dropwise thereto over 1 hour. This reaction solution was stirred at -70° C. for 2 hours and then warmed and saturated aqueous ammonium chloride was added thereto at -20° C. To the reaction mixture, a liquid mixture of ethyl acetate with water was added. The organic layer was washed successively with dilute hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting oily residue was subjected to silica gel column chromatography (Wakogel™ C-300, heptane-ethyl acetate=4:1) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[α-hydroxy-4-(methoxymethoxymethyl)benzyl]pyrrolidine (24.1 g, yield: 59.8%) as a colorless oily substance.

Workup

  1. waitover 1 hour
  2. stirringThis reaction solution was stirred at -70° C. for 2 hours
  3. temperaturewarmed
  4. customat -20° C
  5. additionwas added
  6. washThe organic layer was washed successively with dilute hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-38f7759caa8b4e72bb71a6f115687d08
Source dataset
uspto-grants-1998_01
Patent number
US05707987

Reaction notes

Loading…