2,2,2-Trifluoroethanol → Sitagliptin

HRID 1727447Notes

Reaction equation

HRID 1727447 reaction equation
[O:1]=[C:2]([N:16]1[CH2:21][CH2:20][N:19]2[C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=[C:18]2[CH2:17]1)/[CH:3]=[C:4](\[NH2:15])/[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].FC(F)(F)CO.[H][H]>[B-](F)(F)(F)F.C1C2C=CC1C=C2.C1C2C=CC1C=C2.[Rh].CO>[O:1]=[C:2]([N:16]1[CH2:21][CH2:20][N:19]2[C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=[C:18]2[CH2:17]1)[CH2:3][C@H:4]([NH2:15])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14]

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 29986152Sitagliptin enamineHCID 178418361HCID 178418361, compound

Product 1

HCID 4369359Sitagliptin

Reagents, catalysts & solvents 2

HCID 10915722Bis(norbornadiene)rhodium(I) tetrafluoroborateCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

Into a flask were charged bis(norbornadiene)rhodium(I) tetrafluoroborate {[Rh(nbd)2]BF4}(41.55 mg, 0.1 mmol), Ligand D (69.73 mg, 0.1 mmol) and the enamine amide 2-4 (45 g, 111.1 mmol) under a nitrogen atmosphere. To this mixture a solvent mixture of 37.5 mL methanol (extra dry and degassed) and 112.5 mL 2,2,2-trifluoroethanol (distilled and degassed) were added. The slurry was then transferred under nitrogen into an stainless steel autoclave and sealed. The autoclave was then heated to 50° C. and pressurized to 500 psig with hydrogen. A sample taken after 17 hours was analyzed using HPLC, which confirmed the end of the reaction giving 94% assay yield and 94% ee.

Workup

  1. additionwere added
  2. customsealed
  3. customgiving 94%
  4. customassay yield

Sources & evidence

ORD record
ord-cff681f700be4f089cd0a8a419ea1983
Source dataset
uspto-grants-2009_02
Patent number
US07495123B2

Reaction notes

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