Ammonium formate → (S)-2-[5-(3-Amino-4-ethyl-6-methoxy-5-trifluoromethyl-pyridin-2-yl)-[1,3,4]oxadiazol-2-yl]-1,1,1-trifluoro-propan-2-ol

HRID 574220Notes

Reaction equation

HRID 574220 reaction equation
[NH2:1][C:2]1[C:3]([C:16]2[O:20][C:19]([C@@:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23])=[N:18][N:17]=2)=[N:4][C:5]([O:14][CH3:15])=[C:6]([C:10]([F:13])([F:12])[F:11])[C:7]=1[CH:8]=[CH2:9].C([O-])=O.[NH4+]>CCO.[OH-].[OH-].[Pd+2]>[NH2:1][C:2]1[C:3]([C:16]2[O:20][C:19]([C@@:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23])=[N:18][N:17]=2)=[N:4][C:5]([O:14][CH3:15])=[C:6]([C:10]([F:12])([F:13])[F:11])[C:7]=1[CH2:8][CH3:9]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 86729605(S)-2-(5-(3-Amino-6-methoxy-5-(trifluoromethyl)-4-vinylpyridin-2-yl)-1,3,4-oxadiazol-2-yl)-1,1,1-trifluoropropan-2-ol

Product 1

HCID 71515815(S)-2-[5-(3-Amino-4-ethyl-6-methoxy-5-trifluoromethyl-pyridin-2-yl)-[1,3,4]oxadiazol-2-yl]-1,1,1-trifluoro-propan-2-ol

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

To a stirring solution of (S)-2-(5-(3-amino-6-methoxy-5-(trifluoromethyl)-4-vinylpyridin-2-yl)-1,3,4-oxadiazol-2-yl)-1,1,1-trifluoropropan-2-ol (step 1)(153 mg, 0.384 mmol) in EtOH (10 ml) was added palladium hydroxide on carbon (43.2 mg, 0.307 mmol) followed by ammonium formate (969 mg, 15.37 mmol). The reaction mixture was heated at relux for 30 minutes. The mixture was filtered through Celite® and diluted with EtOAc. The filtrate and washed with sat.NaHCO3, water, brine and dried over MgSO4. Isolute Si-TMT (2,4,6-trimercaptotriazine silica, palladium scavenger) was added the mixture was stirred for 30 mins and filtered. The solvent was removed in vacuo and purification of the crude product by chromatography on silica eluting with 0-30% EtOAc in iso-hexane afforded the title compound;

Workup

  1. temperatureThe reaction mixture was heated at relux for 30 minutes
  2. filtrationThe mixture was filtered through Celite®
  3. additiondiluted with EtOAc
  4. washThe filtrate and washed
  5. dry with materialNaHCO3, water, brine and dried over MgSO4
  6. additionIsolute Si-TMT (2,4,6-trimercaptotriazine silica, palladium scavenger) was added the mixture
  7. filtrationfiltered
  8. customThe solvent was removed in vacuo and purification of the crude product by chromatography on silica eluting with 0-30% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-125ccc7c790f4b94b8333e9e5c3e658d
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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