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 629746ノート

反応式

HRID 629746 の反応式
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]

参加物

4

反応物 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

生成物 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-carboxylate収率 50%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-be4e2b5c8c9546abae752c5cd467e4ef
出典データセット
uspto-grants-2016_04
特許番号
US09315475B2

反応ノート

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