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

HRID 652807Notes

Reaction equation

HRID 652807 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 ; 1H 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 OCH2CH), 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-e0bbd8dc802b44fda669c40b0c2d7fc9
Source dataset
uspto-grants-1987_06
Patent number
US04673737

Reaction notes

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