Ammonium formate → HCID 118307966, compound

HRID 530284Notes

Reaction equation

HRID 530284 reaction equation
[F:1][C:2]1([CH3:22])[CH2:7][C:6]([F:9])([F:8])[C@:5]([C:11]2[CH:16]=[C:15]([N+:17]([O-])=O)[CH:14]=[CH:13][C:12]=2[F:20])([CH3:10])[NH:4][C:3]1=[O:21].C([O-])=O.[NH4+]>CO.[Pd]>[NH2:17][C:15]1[CH:14]=[CH:13][C:12]([F:20])=[C:11]([C@@:5]2([CH3:10])[NH:4][C:3](=[O:21])[C:2]([F:1])([CH3:22])[CH2:7][C:6]2([F:9])[F:8])[CH:16]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 118307918HCID 118307918, compound

Product 1

HCID 118307966HCID 118307966, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(6R)-3,5,5-Trifluoro-6-(2-fluoro-5-nitrophenyl)-3,6-dimethylpiperidin-2-one (2.08 g, 6.50 mmol) (1:1.8 mixture of diastereomers) was dissolved in methanol (28 ml). Ammonium formate (2.05 g, 32.5 mmol) was added followed by portionwise addition of palladium on carbon (1.38 g, 1.30 mmol, 10%). The reaction is slightly exothermic and the reaction mixture was briefly immersed into an ice/water bath to control the temperature increase. After the initial temperature increase had settled, the reaction was stirred at room temperature for another 10 min. The reaction was filtered through a plug of celite using methanol for elution. The filtrate was concentrated under reduced pressure and partitioned between ethyl acetate (100 mL) and saturated aqueous NaHCO3 (50 mL). The phases were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organics were dried over MgSO4, filtered and concentrated under reduced pressure to afford (6R)-6-(5-amino-2-fluorophenyl)-3,5,5-trifluoro-3,6-dimethylpiperidin-2-one (1.73 g, 5.96 mmol, 92% yield) (1:1.8 mixture of diastereomers). LC-MS Major: (m/z) 291.0 (MH+-tert-butyl) tR=0.40 minutes (Method B); Minor: (m/z) 291.0 (MH+) tR=0.41 minutes (Method B). The crude material was used in the next reaction step without further purification.

Workup

  1. customthe reaction mixture was briefly immersed into an ice/water bath
  2. temperatureincrease
  3. temperatureAfter the initial temperature increase
  4. filtrationThe reaction was filtered through a plug of celite
  5. washfor elution
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompartitioned between ethyl acetate (100 mL) and saturated aqueous NaHCO3 (50 mL)
  8. customThe phases were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  10. dry with materialThe combined organics were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1b655eff21a545c5b481eb607b0558fa
Source dataset
uspto-grants-2016_05
Patent number
US09353084B2

Reaction notes

Loading…