Ethyl Acetate → (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[alpha-hydroxy-3-(tetrahydropyranyloxymethyl)benzyl]pyrrolidine

HRID 725953

Reaction equation

HRID 725953 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]1[CH:10]=[C:11](Br)[CH:12]=[CH:13][CH:14]=1.[C:16]([O:20][C:21]([N:23]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:24]1[CH:25]=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1.O>[C:16]([O:20][C:21]([N:23]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:24]1[CH:25]([OH:26])[C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH:10]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 152820642-[(3-Bromophenyl)methoxy]oxane

Product 1

HCID 22881079(2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[alpha-hydroxy-3-(tetrahydropyranyloxymethyl)benzyl]pyrrolidineYield 55.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 3-(tetrahydropyranyloxymethyl)bromobenzene (11.8 g, 43.5 mmol) in tetrahydrofuran (20 ml) was added dropwise to a solution of 1.6M n-butyl lithium-hexane solution (30 ml, 48 mmol) in tetrahydrofuran (100 ml) at -78° C. in a nitrogen stream over 15 minutes. This reaction solution was stirred at -78° C. for 40 minutes and then a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (7.2 g, 21.9 mmol) in tetrahydrofuran (20 ml) was added dropwise over 20 minutes. The reaction solution was stirred at -78° C. for 30 minutes and then allowed to gradually warm and saturated aqueous ammonium chloride was added thereto. This solution was poured into a liquid mixture of ethyl acetate with water and 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, heptane-ethyl acetate=6:1) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[α-hydroxy-3-(tetrahydropyranyloxymethyl)benzyl]pyrrolidine (6.3 g, yield: 55.0%) as a yellow oily substance.

Workup

  1. stirringThe reaction solution was stirred at -78° C. for 30 minutes
  2. temperatureto gradually warm
  3. washthe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e0ba0091955a41b9a9522f8562e011bf
Source dataset
uspto-grants-1998_01
Patent number
US05707987

Linked notes

Loading…