Ammonium Hydroxide → HCID 131733577, compound

HRID 1749404Notes

Reaction equation

HRID 1749404 reaction equation
[CH3:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[OH-].[NH4+].CCN(C(C)C)C(C)C.[O:25](C(OC(C)(C)C)=O)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=O>CO.[Ni].C(Cl)Cl>[CH3:1][C:2]1[N:3]=[CH:4][C:5]([CH2:6][NH:7][C:26](=[O:25])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[C:8]([C:10]([F:11])([F:13])[F:12])[CH:9]=1

Participants

8

Reactant 4

HCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 27809766-methyl-4-(trifluoromethyl)nicotinonitrile

Product 1

HCID 131733577HCID 131733577, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

6-Methyl-4-(trifluoromethyl)nicotinonitrile (1.0 equiv.) was dissolved in MeOH (0.1 M), wet Raney nickel was added, followed by ammonium hydroxide (32 equiv.). The reaction vessel was evacuated three times, refilled with hydrogen and then equipped with a hydrogen balloon and stirred at room temperature for 48 h. The mixture was filtered through a short pad of celite which was washed with MeOH. Ethanol was added to remove excess water upon concentration. The volatile solvents were removed to afford crude product which was dissolved in DCM. DIEA (1.8 equiv.) was added followed by BOC2O (0.95 equiv.). The reaction was stirred at room temperature for 1 h. The volatile solvent was removed and the residue was purified via Biotage chromatography (10-100% ethyl acetate in hexanes) to afford tert-butyl ((6-methyl-4-(trifluoromethyl)pyridin-3-yl)methyl)carbamate (90% yield); MS(ESI) m/z 290.3[M+1]+

Workup

  1. customThe reaction vessel was evacuated three times
  2. additionrefilled with hydrogen
  3. customequipped with a hydrogen balloon
  4. filtrationThe mixture was filtered through a short pad of celite which
  5. washwas washed with MeOH
  6. additionEthanol was added
  7. customto remove excess water
  8. concentrationupon concentration
  9. customThe volatile solvents were removed
  10. customto afford crude product which
  11. stirringThe reaction was stirred at room temperature for 1 h
  12. customThe volatile solvent was removed
  13. customthe residue was purified via Biotage chromatography (10-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2074697ea3194d3e9dd5b40d46dfba8b
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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