Ethyl bromoacetate → (S)-(+)-2-Oxo-4-phenyl-3-oxazolidineacetic acid

HRID 1608310Notes

Reaction equation

HRID 1608310 reaction equation
[C:1]1([C@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:16][C:17]([O:19]CC)=[O:18].[OH-].[Na+]>C1COCC1>[C:1]1([C@H:7]2[CH2:11][O:10][C:9](=[O:12])[N:8]2[CH2:16][C:17]([OH:19])=[O:18])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 7304242-Oxazolidinone, 4-phenyl-, (4S)-

Product 1

HCID 853681(S)-(+)-2-Oxo-4-phenyl-3-oxazolidineacetic acidYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred, 0° C. solution of (S)-4-phenyloxazoldin-2-one (1.07 g, 6.54 mmol) in 15 mL of THF was added sodium hydride (0.32 g of a 60% oil dispersion, 8.0 mmol). When gas evolution had ceased (ca. 10 minutes), ethyl bromoacetate (0.87 mL, 7.8 mmol) was added. After 2 hours at 0° C., the mixture was treated with 50 mL of 2N aqueous NaOH, stirred rapidly for 1 hour at room temperature, and then partitioned between hexane (50 mL) and water (50 mL). The aqueous layer was separated, acidified with 6M aqueous H2SO4, and extracted with dichloromethane (2×200 mL). The combined organic phases were dried (Na2SO4) and concentrated to a thick oil, which was dissolved in 4 mL of warm toluene, seeded, and allowed to crystallize overnight; filtration gave 1.33 g (92%) of (S)-4-phenyloxazolidin-2-one-3-ylacetic acid: mp 106°-108° C.; [α]D22 +173° (c=2.0, CHCl3); IR (CHCl3) 3500-2500 (v. br), 1760 (br), 1480, 1460, 1430, 1230 cm-1 ; 2H NMR δ11.2 (br s, 1, COOH), 7.47-7.25 (m, 5, ArH), 5.05 (t, 1, J=8.4 Hz, OCH2CH), 4.72 (t, 1, J=8.8 Hz, one of OCH2CH), 4.32 (d, 1, J=18.4 Hz, one of NCH2), 4.17 (t, 1, J=8.4 Hz, one of OCH 2CH), 3.41 (d, 1, J=18.4 Hz, one of NCH2).

Workup

  1. additionwas added
  2. custompartitioned between hexane (50 mL) and water (50 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with dichloromethane (2×200 mL)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. concentrationconcentrated to a thick oil, which
  7. dissolutionwas dissolved in 4 mL of warm toluene
  8. customto crystallize overnight
  9. filtrationfiltration

Sources & evidence

ORD record
ord-c1101b3789a54bd8bca7c1c3dd483511
Source dataset
uspto-grants-1989_09
Patent number
US04870169

Reaction notes

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