Diisopropylamine → (4S)-2,2-Dimethyl-4-((E)-3-phenyl-but-2-enyl)-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 885163Notes

Reaction equation

HRID 885163 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCOP(OCC)([CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:19])=O.[C:29]([O:33][C:34]([N:36]1[C@@H:40]([CH2:41][CH:42]=O)[CH2:39][O:38][C:37]1([CH3:45])[CH3:44])=[O:35])([CH3:32])([CH3:31])[CH3:30]>O1CCCC1>[C:29]([O:33][C:34]([N:36]1[C@@H:40]([CH2:41]/[CH:42]=[C:18](/[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)\[CH3:19])[CH2:39][O:38][C:37]1([CH3:44])[CH3:45])=[O:35])([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 99789Diethyl P-(1-phenylethyl)phosphonateHCID 10586317(S)-Tert-butyl 2,2-dimethyl-4-(2-oxoethyl)oxazolidine-3-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67177964(4S)-2,2-Dimethyl-4-((E)-3-phenyl-but-2-enyl)-oxazolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N,N-diisopropylamine (1.74 ml) in tetrahydrofuran (8 ml) at −78° C. was added dropwise a solution of n-butyllithium (7.71 ml, 1.6 M in hexane) and the reaction mixture was then warmed to 0° C. for 15 min. After re-cooling to −78° C., a solution of diethyl 1-phenylethyl phosphonate (2.76 ml) in tetrahydrofuran (8 ml) was added dropwise. The mixture was stirred at −78° C. for 30 min and then a solution of (S)-2,2-dimethyl-4-(2-oxo-ethyl)-oxazolidine-3-carboxylic acid tert-butyl ester (2.00 g, CAS 147959-19-1) in tetrahydrofuran (8 ml) was added dropwise over 20 min. The mixture was then allowed to warm to room temperature and stirring continued at room temperature for 48 hours. The mixture was then quenched by addition of aqueous hydrochloric acid (2N) and then made basic by addition of aqueous sodium hydroxide solution (1 N). The mixture was taken up in ethyl acetate and the phases separated. The organic layer was washed sequentially with water and with saturated brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (SiO2, heptane/EtOAc gradient) to yield a yellow oil, (1.16 g, 44%); MS (ISP): 332.1 ([M+H]+).

Workup

  1. temperatureAfter re-cooling to −78° C.
  2. temperatureto warm to room temperature
  3. stirringstirring
  4. waitcontinued at room temperature for 48 hours
  5. customThe mixture was then quenched by addition of aqueous hydrochloric acid (2N)
  6. additionmade basic by addition of aqueous sodium hydroxide solution (1 N)
  7. customthe phases separated
  8. washThe organic layer was washed sequentially with water and with saturated brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography (SiO2, heptane/EtOAc gradient)
  12. customto yield a yellow oil, (1.16 g, 44%)

Sources & evidence

ORD record
ord-c9ced7e09b194fc4b7644ceab3b75a34
Source dataset
uspto-grants-2012_08
Patent number
US08242153B2

Reaction notes

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