Tetrahydrofuran → (5R)-3-(4-benzyloxy-3-fluoro-phenyl)-5-hydroxy-methyl-oxazolidin-2-one

HRID 1888854Notes

Reaction equation

HRID 1888854 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:13]([F:25])[CH:12]=1)[C:2]1C=CC=C[CH:3]=1.C([Li])CCC.CCCCCC.[O:38]1CCCC1>>[CH2:18]([O:17][C:14]1[CH:15]=[CH:16][C:11]([N:10]2[CH:2]([CH3:3])[C@H:1]([OH:38])[O:8][C:9]2=[O:26])=[CH:12][C:13]=1[F:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8058HexaneHCID 57754845Benzyl [4-(benzyloxy)-3-fluorophenyl]carbamateHCID 178418339Butyllithium

Product 1

HCID 67279383(5R)-3-(4-benzyloxy-3-fluoro-phenyl)-5-hydroxy-methyl-oxazolidin-2-one

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 17.5 g (4-benzyloxy-3-fluoro-phenyl)-carbamic acid benzyl ester (MW: 351.38, 50 mmol) in 30 ml of dry tetrahydrofuran was cooled to −78° C. with a dry ice/acetone bath. 22.8 ml of a 2.3M n-butyl-lithium solution in n-hexane (52.5 mmol) was added drop wise and the reaction mixture stirred at −78° C. for 15 min. 7.92 g R(−)-glycidyl butyrate (MW: 144.17, 60 mmol) were added and the reaction was allowed to warm up to room temperature. The reaction was monitored by HPLC, quenched with a saturated ammonium chloride solution and diluted with 100 ml of ethyl acetate. The organic layer was washed with 200 ml water and 200 ml brine. The organic layer was dried over magnesium sulfate, filtered and the filtrate evaporated under reduced pressure. The residue was crystallized from 200 ml of a 1/1-ethyl acetate/hexane mixture. The solid was collected and recrystallized from 150 ml of a 9/1 ethyl acetate/dichloro-methane mixture. The colorless crystals were collected and dried. Yield: 10.4-g, 65.5%. MS: 318.1 (M+H)+. Method ESI+.

Workup

  1. temperatureto warm up to room temperature
  2. customquenched with a saturated ammonium chloride solution
  3. additiondiluted with 100 ml of ethyl acetate
  4. washThe organic layer was washed with 200 ml water and 200 ml brine
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. customthe filtrate evaporated under reduced pressure
  8. customThe residue was crystallized from 200 ml of a 1/1-ethyl acetate/hexane mixture
  9. customThe solid was collected
  10. customrecrystallized from 150 ml of a 9/1 ethyl acetate/dichloro-methane mixture
  11. customThe colorless crystals were collected
  12. customdried

Sources & evidence

ORD record
ord-df9d6d483cfa436f8084f2d888c780d1
Source dataset
uspto-grants-2013_08
Patent number
US08501774B2

Reaction notes

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