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 629746Notes

Reaction equation

HRID 629746 reaction equation
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]

Participants

4

Reactant 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

Product 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-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-be4e2b5c8c9546abae752c5cd467e4ef
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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