Phosphate → (4S)-3-[(2S)-2-(biphenyl-4-ylmethoxy)propanoyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one

HRID 1023273Notes

Reaction equation

HRID 1023273 reaction equation
C([Li])CCC.[CH3:6][C:7]1([CH3:19])[O:11][C:10](=[O:12])[NH:9][C@H:8]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:20]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:25]=[CH:24][C:23]([CH2:26][O:27][C@@H:28]([CH3:32])[C:29](Cl)=[O:30])=[CH:22][CH:21]=1.P([O-])([O-])([O-])=O>O1CCCC1>[C:20]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:25]=[CH:24][C:23]([CH2:26][O:27][C@@H:28]([CH3:32])[C:29]([N:9]2[C@@H:8]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:7]([CH3:19])([CH3:6])[O:11][C:10]2=[O:12])=[O:30])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 1061PhosphateHCID 2733820(S)-(+)-5,5-Dimethyl-4-phenyl-2-oxazolidinoneHCID 86655561(2S)-2-(biphenyl-4-ylmethoxy)propanoyl chlorideHCID 178418339Butyllithium

Product 1

HCID 58354503(4S)-3-[(2S)-2-(biphenyl-4-ylmethoxy)propanoyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A butyllithium solution (9.7 M in hexanes, 7.64 mL, 74 mmol) was added drop-wise to a solution of C3 (13.5 g, 70.6 mmol) in tetrahydrofuran (800 mL) at −78° C., and the mixture was stirred for 30 minutes at −78° C., A solution of C6 (21.3 g, 78 mmol) in tetrahydrofuran (50 mL) was then added slowly, and the reaction was stirred at −78° C. for 30 minutes and then at 25° C. for about 3 hours. The reaction mixture was then poured into phosphate buffer (pH 7) and extracted with ethyl acetate (2×). The organic extract was washed with aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to a minimal volume. The resultant residue was then precipitated by addition of 1 liter of hexanes. The solid white product was collected by filtration, and the filtrate was concentrated. The resultant residue was purified by silica gel chromatography (gradient: 9:1 hexanes:ethyl acetate to 6:4 hexanes:ethyl acetate), to provide C7 as a white solid. Yield: 22.8 g, 75 LCMS m/z 430.3 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 0.85 (3H, s), 1.35 (3H, d, J=6.6 Hz), 1.57 (3H, s), 4.36 (2H, apparent s, actual AB quartet, J=12.3 Hz), 5.21 (1H, s), 5.21 (1H, q, J=6.6 Hz), 7.23 (2H, m), 7.38 (8H, m), 7.61 (4H, m).

Workup

  1. stirringthe reaction was stirred at −78° C. for 30 minutes
  2. waitat 25° C. for about 3 hours
  3. extractionextracted with ethyl acetate (2×)
  4. extractionThe organic extract
  5. washwas washed with aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to a minimal volume
  8. customThe resultant residue was then precipitated by addition of 1 liter of hexanes
  9. filtrationThe solid white product was collected by filtration
  10. concentrationthe filtrate was concentrated
  11. customThe resultant residue was purified by silica gel chromatography (gradient: 9:1 hexanes:ethyl acetate to 6:4 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-74a610a1dde44d329ca24e140d910157
Source dataset
uspto-grants-2014_05
Patent number
US08722686B2

Reaction notes

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