2,2,2-Trifluoroethanol → Sitagliptin

HRID 1727446Notes

Reaction equation

HRID 1727446 reaction equation
C(O)C(F)(F)F.[O:7]=[C:8]([N:22]1[CH2:27][CH2:26][N:25]2[C:28]([C:31]([F:34])([F:33])[F:32])=[N:29][N:30]=[C:24]2[CH2:23]1)/[CH:9]=[C:10](\[NH2:21])/[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[CH:14][C:13]=1[F:20]>>[O:7]=[C:8]([N:22]1[CH2:27][CH2:26][N:25]2[C:28]([C:31]([F:34])([F:33])[F:32])=[N:29][N:30]=[C:24]2[CH2:23]1)[CH2:9][C@H:10]([NH2:21])[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[CH:14][C:13]=1[F:20]

Participants

3

Reactant 2

HCID 64092,2,2-TrifluoroethanolHCID 29986152Sitagliptin enamine

Product 1

HCID 4369359Sitagliptin

Procedure

Into a flask was charged [Rh(cod)2]OTf (0.1 mmol) and (S)-Cy2-p-Tol-Biphemp (Ligand E) (0.1 mmol) under a nitrogen atmosphere. Degassed trifluoroethanol was then added (20 mL) and the mixture was stirred at room temperature for 1 h. Into a hydrogenator was charged the enamine amide 2-4 (1 mmol) and then degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 100 psig hydrogen gas at 20° C. for 20 h (94% assay yield, 98% ee).

Workup

  1. customdegassed
  2. customAfter degassing three times
  3. waitthe enamine amide was hydrogenated under 100 psig hydrogen gas at 20° C. for 20 h

Sources & evidence

ORD record
ord-4c375537b4c747d2b29001279c2939fb
Source dataset
uspto-grants-2009_02
Patent number
US07495123B2

Reaction notes

Loading…