Pivaloyl chloride → (R)-4-benzyl-3-(2-(4-chloro-3-fluorophenyl)acetyl)oxazolidin-2-one

HRID 532517Notes

Reaction equation

HRID 532517 reaction equation
CC(C)(C)C(Cl)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=O)=[CH:11][C:10]=1[F:19].[Li]CCCC.[CH2:25]([C@@H:32]1[CH2:36][O:35][C:34](=[O:37])[NH:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[CH2:25]([C@@H:32]1[CH2:36][O:35][C:34](=[O:37])[N:33]1[C:16](=[O:18])[CH2:15][C:12]1[CH:13]=[CH:14][C:9]([Cl:8])=[C:10]([F:19])[CH:11]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 62493Pivaloyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinone2×HCID 38149542-(4-Chloro-3-fluorophenyl)acetic acidHCID 178418339Butyllithium

Product 1

HCID 59580359(R)-4-benzyl-3-(2-(4-chloro-3-fluorophenyl)acetyl)oxazolidin-2-oneYield 60.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Trimethylacetyl chloride (1.68 g, 13.9 mmol) was added to a solution of 2-(4-chloro-3-fluorophenyl)acetic acid (2.50 g, 13.3 mmol) and TEA (d. 0.726; 2.00 mL, 14.3 mmol) in dry THF (100 mL) at 0° C. and stirred at room temperature. In a separate flask, n-BuLi (6.424 mL, 14.58 mmol) was added to (R)-4-benzyloxazolidin-2-one (2.47 g, 13.9 mmol) in dry THF (100 mL) at −78° C. The reaction was strirred for 20 minutes at −78° C., and then the (R)-4-benzyloxazolidin-2-one solution was added dropwise to the 0° C. mixed anhydride solution. The reaction was allowed to stir overnight at room temperature. The reaction was quenched with water (100 mL) and diluted with ethyl acetate (100 mL). The layers were separated, and the organics were washed with brine, dried (MgSO4) and concentrated to a residue. The resulting residue was purified by flash chromatography to give (R)-4-benzyl-3-(2-(4-chloro-3-fluorophenyl)acetyl)oxazolidin-2-one (2.79 g, 8.02 mmol, 60.5% yield). 1H NMR (400 MHz, CDCl3) 7.37 (t, J=8.2 Hz, 1H), 7.33-7.26 (m, 3H), 7.18-7.12 (m, 3H), 7.07 (d, J=8.2 Hz, 1H), 4.73-4.65 (m, 1H), 4.33-4.18 (m, 4H), 3.27 (dd, J1=3.5 Hz, J2=13.3 Hz, 1H), 2.77 (dd, J1=9.4 Hz, J2=13.7 Hz, 1H).

Workup

  1. stirringto stir overnight at room temperature
  2. customThe reaction was quenched with water (100 mL)
  3. additiondiluted with ethyl acetate (100 mL)
  4. customThe layers were separated
  5. washthe organics were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated to a residue
  8. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-75fc89cd48ad44c6b1c16345b9e171b1
Source dataset
uspto-grants-2014_10
Patent number
US08853216B2

Reaction notes

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