Tetrabutylammonium Fluoride → tert-butyl (2S,5R)-2-[(2-{[N-(tert-butoxycarbonyl)-4-fluoro-beta-(4-fluorophenyl)-L-phenylalanyl]amino}-6-fluorophenoxy)methyl]-5-(hydroxymethyl)morpholine-4-carboxylate

HRID 629746노트

반응식

HRID 629746 반응식
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[C:19]([O:23][C:24]([NH:26][C@H:27]([C:43]([NH:45][C:46]1[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[C:47]=1[O:48][CH2:49][C@H:50]1[O:55][CH2:54][C@@H:53]([CH2:56][O:57][Si](C(C)(C)C)(C)C)[N:52]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:51]1)=[O:44])[CH:28]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>C1COCC1>[C:19]([O:23][C:24]([NH:26][C@H:27]([C:43]([NH:45][C:46]1[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[C:47]=1[O:48][CH2:49][C@H:50]1[O:55][CH2:54][C@@H:53]([CH2:56][OH:57])[N:52]([C:65]([O:67][C:68]([CH3:69])([CH3:70])[CH3:71])=[O:66])[CH2:51]1)=[O:44])[CH:28]([C:29]1[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=1)[C:36]1[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=1)=[O:25])([CH3:20])([CH3:21])[CH3:22]

참가 물질

4

반응물 2

HCID 2724141Tetrabutylammonium FluorideHCID 86726345tert-butyl (2S,5S)-2-[(2-{[N-(tert-butoxycarbonyl)-4-fluoro-beta-(4-fluorophenyl)-L-phenylalanyl]amino}-6-fluorophenoxy)methyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

생성물 1

HCID 86726346tert-butyl (2S,5R)-2-[(2-{[N-(tert-butoxycarbonyl)-4-fluoro-beta-(4-fluorophenyl)-L-phenylalanyl]amino}-6-fluorophenoxy)methyl]-5-(hydroxymethyl)morpholine-4-carboxylate수율 50%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

1M TBAF (1766 μl, 1.766 mmol) in THF was added to a solution of tert-butyl (2S,5S)-2-[(2-{[N-(tert-butoxycarbonyl)-4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]amino}-6-fluorophenoxy)methyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate (977 mg, 1.177 mmol) in THF (5.89 mL) at room temperature and the reaction stirred at room temperature until completion (6 hours). The reaction was quenched with a saturated aqueous solution of KH2PO4 and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic fractions were dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. The crude material was then purified on silica gel (120 g), eluting with a gradient of 0-100% a 7:2:1 CHCl3/EtOAc/MeOH blend in CHCl3 to afford the title compound (439 mg, 0.589 mmol, 50% yield) as a white foam, MS (ESI): m/z=616.4 (M+H-boc); 96% pure by LC/MS.

후처리

  1. customThe reaction was quenched with a saturated aqueous solution of KH2PO4
  2. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic fractions were dried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe crude material was then purified on silica gel (120 g)
  7. washeluting with a gradient of 0-100% a 7:2:1 CHCl3/EtOAc/MeOH

출처 및 근거

ORD 기록
ord-be4e2b5c8c9546abae752c5cd467e4ef
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315475B2

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