tert-Butyl (2R,5S)-2-[(3-amino-5-fluoropyridin-4-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate → Tert-butyl (2R,5S)-2-(2-(3-amino-5-fluoropyridin-4-YL)ethyl)-5-(((tert-butyldimethylsilyl)oxy)methyl)morpholine-4-carboxylate

HRID 629736Notes

Reaction equation

HRID 629736 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:32])[C:7]=1[C:8]#[C:9][C@H:10]1[O:15][CH2:14][C@@H:13]([CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[N:12]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:11]1>[Pt](=O)=O>[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:32])[C:7]=1[CH2:8][CH2:9][C@H:10]1[O:15][CH2:14][C@@H:13]([CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[N:12]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:11]1

Participants

3

Reactant 1

HCID 86726336tert-Butyl (2R,5S)-2-[(3-amino-5-fluoropyridin-4-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

Product 1

HCID 86726335Tert-butyl (2R,5S)-2-(2-(3-amino-5-fluoropyridin-4-YL)ethyl)-5-(((tert-butyldimethylsilyl)oxy)methyl)morpholine-4-carboxylateYield 69%

Reagents, catalysts & solvents 1

HCID 345198Adams' catalystCatalyst

Procedure

Platinum(IV) oxide (0.536 g, 2.36 mmol) was suspended in nitrogen degassed trifluororoethanol. tert-Butyl (2R,5S)-2-[(3-amino-5-fluoropyridin-4-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate (2.20 g, 4.72 mmol) (68% pure) was dissolved in nitrogen degassed trifluorethanol (94 mL) and added to the suspension of platinum oxide. The reaction was shaken on the Parr at 50 psi hydrogen for 24 hr. The reaction was degassed with nitrogen, filtered through celite and the solvent removed in vacuo. Purification on silica gel (330 g) eluting with a gradient of 0-100% EtOAc/hexanes afforded the title compound (1.52 g, 3.24 mmol, 69% yield) as a white solid, MS (ESI): m/z=470.51 (MH+); 100% pure by LCMS

Workup

  1. customdegassed trifluorethanol (94 mL)
  2. additionadded to the suspension of platinum oxide
  3. customThe reaction was degassed with nitrogen
  4. filtrationfiltered through celite
  5. customthe solvent removed in vacuo
  6. customPurification on silica gel (330 g)
  7. washeluting with a gradient of 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-61cea303fb84485ba68bc885caa762fb
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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