Sodium hydride → (R)-6-fluoro-3-(3-oxiranylmethoxy-phenyl)-benzo[d]isoxazole

HRID 852082Notes

Reaction equation

HRID 852082 reaction equation
[H-].[Na+].CC1C=CC(S(O[CH2:14][C@@H:15]2[O:17][CH2:16]2)(=O)=O)=CC=1.[F:18][C:19]1[CH:34]=[CH:33][C:22]2[C:23]([C:26]3[CH:27]=[C:28]([OH:32])[CH:29]=[CH:30][CH:31]=3)=[N:24][O:25][C:21]=2[CH:20]=1>CN(C)C=O.O>[F:18][C:19]1[CH:34]=[CH:33][C:22]2[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:14][C@H:15]4[CH2:16][O:17]4)[CH:27]=3)=[N:24][O:25][C:21]=2[CH:20]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 154187Glycidyl tosylate, (R)-HCID 179062783-(6-Fluoro-benzo[d]isoxazol-3-yl)-phenol

Product 1

HCID 58928264(R)-6-fluoro-3-(3-oxiranylmethoxy-phenyl)-benzo[d]isoxazoleYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

The title compound is prepared from a mixture of sodium hydride in dimethylformamide, 3-(6-fluoro-benzo[d]isoxazol-3-yl)-phenol in dimethylformamide and (2R)-(−)-glycidyl tosylate in dimethylformamide essentially as described above except that the reaction mixture is diluted with water, extracted with ethyl acetate, washed with water (twice), dried (MgSO4), concentrated and purified by column (silica) chromatography eluting with a graded solvent mixtures of toluene to 1% ether in toluene to give the title compound as a white solid (9.29 g, 75% Yield). NMR and microanalysis (C, H, N) are consistent with the final, desired compound. Chiral HPLC, 16.92 minutes, [Chiralcel OD (250×4.6 mm), 98:2 heptane/ethanol @ 0.8 mL/min, UV @ 285 nm, 18.14] shows the title compound as 95.5% e.e. mp=84-85° C.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with water (twice),
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by column (silica) chromatography
  6. washeluting with a graded solvent mixtures of toluene to 1% ether in toluene

Sources & evidence

ORD record
ord-f56359d30b3d4c5ea6c7af588a836c59
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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