Acetohydroxamic Acid → {3-amino-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzisoxazol-5-yl}methanol

HRID 245354

반응식

HRID 245354 반응식
[Si]([O:18][CH2:19][C:20]1[C:21]([N:30]2[CH2:35][C@H:34]([CH3:36])[O:33][C@H:32]([CH3:37])[CH2:31]2)=[C:22]([F:29])[C:23](F)=C([CH:27]=1)C#N)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])(C)C.[K+].[C:44]([NH:47][OH:48])(=O)[CH3:45].C[N:50](C=O)C>CCOC(C)=O>[NH2:50][C:44]1[C:45]2[CH:27]=[C:20]([CH2:19][OH:18])[C:21]([N:30]3[CH2:31][C@H:32]([CH3:37])[O:33][C@H:34]([CH3:36])[CH2:35]3)=[C:22]([F:29])[C:23]=2[O:48][N:47]=1

참가 물질

6

반응물 4

HCID 1990Acetohydroxamic AcidHCID 6228DimethylformamideHCID 23665647Potassium tert-butoxideHCID 866580455-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorobenzonitrile2회

생성물 1

HCID 67359017{3-amino-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzisoxazol-5-yl}methanol

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

To an ice-bath cooled and stirred solution of 5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorobenzonitrile (Intermediate 6, 500 mg, 0.96 mmol) in DMF was added t-BuOK (161 mg, 1.4 mmol) followed by acetohydroxamic acid (108 mg, 1.4 mmol). The mixture was brought to room temperature and stirred for 12 hours. The reaction mixture was diluted with EtOAc and washed successively with 1 N HCl (1×250 mL), water and brine. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified over silica gel flash column using a gradient of ethyl acetate in pet. ether to give the title compound as a white solid. Yield: 200 mg, (70%).

후처리

  1. temperatureTo an ice-bath cooled
  2. customwas brought to room temperature
  3. washwashed successively with 1 N HCl (1×250 mL), water and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified over silica gel flash column

출처 및 근거

ORD 기록
ord-9150b07950a3457184f55072f551a817
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658641B2

연결된 노트

불러오는 중…