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

HRID 852082노트

반응식

HRID 852082 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매3회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f56359d30b3d4c5ea6c7af588a836c59
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07253165B2

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