Tetrahydrofuran → (R)-(-)-N-Carbobenzyloxy-3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine

HRID 1740179Notes

Reaction equation

HRID 1740179 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[C:6]([N:16]1[CH2:19][CH:18]([C:20]2[CH:36]=[CH:35][C:23]([NH:24][C:25]([O:27][CH2:28][C:29]3C=CC=CC=3)=[O:26])=[CH:22][C:21]=2[F:37])[CH2:17]1)([O:8][CH2:9][C:10]1[CH:15]=CC=CC=1)=[O:7].C1C[O:41][CH2:40]C1>CCCCCC>[C:6]([N:16]1[CH2:19][CH:18]([C:20]2[CH:36]=[CH:35][C:23]([N:24]3[CH2:29][C@H:28]([CH2:40][OH:41])[O:27][C:25]3=[O:26])=[CH:22][C:21]=2[F:37])[CH2:17]1)([O:8][CH2:9][C:10]1[CH:15]=[CH:4][CH:3]=[CH:2][CH:1]=1)=[O:7]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 22625683N-Carbobenzyloxy-3-(N-carbobenzyloxy-3-fluoroanilin-4-yl)azetidineHCID 178418339Butyllithium

Product 1

HCID 21967688(R)-(-)-N-Carbobenzyloxy-3-[2-fluoro-4-[5-hydroxymethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

n-Butyllithium (5.25 mL of a 1.6M solution in hexane, 8.40 mmol) was added dropwise to a stirred solution of N-carbobenzyloxy-3-(N-carbobenzyloxy-3-fluoroanilin-4-yl)azetidine (Example 81, Step 4, 3.63 g, 8.36 mmol) at -78° under nitrogen in dry THF (30 mL), then stirred for 2 hr. a solution of R-glycidyl butyrate (1.21 g, 8.40 mmol) in dry THF (3.0 mL) was added and the cooling bath removed after 15 min. After 18 hr, the solvent was removed and the residue partitioned between ethyl acetate (150 mL) and saturated ammonium chloride solution (50 mL). The organic layer was washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and evaporated leaving an amber oil. Chromatography over silica gel (150 g, 40-60 μm) eluting with 2-5% methanol-chloroform gave the title compound as a sticky foam. FAB-HRMS: theory 401.1513 (M+1); meas 401.1521.

Workup

  1. customthe cooling bath removed after 15 min
  2. waitAfter 18 hr
  3. customthe solvent was removed
  4. customthe residue partitioned between ethyl acetate (150 mL) and saturated ammonium chloride solution (50 mL)
  5. washThe organic layer was washed with water (50 mL) and brine (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customleaving an amber oil
  10. washChromatography over silica gel (150 g, 40-60 μm) eluting with 2-5% methanol-chloroform

Sources & evidence

ORD record
ord-87ad6befa90c4913b911141cb7d6e77e
Source dataset
uspto-grants-1999_10
Patent number
US05968962

Reaction notes

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