Diethyl P-(1-phenylethyl)phosphonate → (S)-2,2-dimethyl-4-((E)-2-phenyl-propenyl)-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1911504Notes

Reaction equation

HRID 1911504 reaction equation
CCOP(OCC)([CH:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:7])=O.C([Li])CCC.[C:22]([O:26][C:27]([N:29]1[C@@H:33]([CH:34]=O)[CH2:32][O:31][C:30]1([CH3:37])[CH3:36])=[O:28])([CH3:25])([CH3:24])[CH3:23]>COCCOC>[C:22]([O:26][C:27]([N:29]1[C@@H:33](/[CH:34]=[C:6](/[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)\[CH3:7])[CH2:32][O:31][C:30]1([CH3:36])[CH3:37])=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 99789Diethyl P-(1-phenylethyl)phosphonateHCID 1787923-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)-HCID 178418339Butyllithium

Product 1

HCID 68710162(S)-2,2-dimethyl-4-((E)-2-phenyl-propenyl)-oxazolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of diethyl 1-phenylethyl phosphonate (2.35 ml) in 1,2-dimethoxyethane (15 ml) was cooled under an argon atmosphere to 0° C. and treated dropwise with an n-butyllithium solution (5.9 ml; 1.6 M in hexane). The reaction mixture was stirred for 5 min at 0° C., then treated dropwise with a solution of (R)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.5 g) in 1,2-dimethoxyethane (15 ml). The solution was warmed to r.t., then refluxed overnight. After cooling to r.t., the mixture was quenched with water and extracted with EtOAc. The organic layer was dried over MgSO4, filtrated and concentrated. The crude product was isolated by column chromatography (SiO2; gradient: cyclohexane ->cyclohexane/EtOAc 1:1) to give (S)-2,2-dimethyl-4-((E)-2-phenyl-propenyl)-oxazolidine-3-carboxylic acid tert-butyl ester (720 mg) as light yellow viscous oil.

Workup

  1. temperatureThe solution was warmed to r.t.
  2. temperaturerefluxed overnight
  3. temperatureAfter cooling to r.t.
  4. customthe mixture was quenched with water
  5. extractionextracted with EtOAc
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltrated
  8. concentrationconcentrated
  9. customThe crude product was isolated by column chromatography (SiO2; gradient: cyclohexane ->cyclohexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-c2e25b2159f046ce957ed7b3d4573e1e
Source dataset
uspto-grants-2013_12
Patent number
US08604061B2

Reaction notes

Loading…