Ammonium formate → HCID 25166502, compound

HRID 1177916Notes

Reaction equation

HRID 1177916 reaction equation
C([O-])=O.[NH4+].[O:5]=[C:6]([N:31]1[CH2:36][CH2:35][N:34]([C:37](=[O:48])[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:44]([F:47])([F:46])[F:45])[CH2:33][CH2:32]1)[CH2:7][NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23]CC2C=CC=CC=2)=[CH:13][CH:12]=1)=[O:10]>CO.O.[Pd]>[O:5]=[C:6]([N:31]1[CH2:36][CH2:35][N:34]([C:37](=[O:48])[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:44]([F:46])([F:47])[F:45])[CH2:33][CH2:32]1)[CH2:7][NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[OH:23])=[CH:13][CH:12]=1)=[O:10]

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 59559671HCID 59559671, compound

Product 1

HCID 25166502HCID 25166502, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Ammonium formate (350 mg, 5.5 mmol) was added to a stirred solution of 2′-Benzyloxy-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide (prepared by the method as described above) (156 mg, 0.26 mmol) in a mixture of MeOH (10 mL) and water (2 ml). 10% Pd/c (40 mg) was then added and the resulting mixture stirred at room temperature under an inert atmosphere. The reaction mixture was then stirred at reflux temperature for 3 hrs. The mixture was filtered over a bed of celite. The celite was washed with MeOH and the filtrate was concentrated. The residue was dissolved in EtOAc, washed with 5% aqueous NaOH solution, followed by saturated brine solution. The organic layer was dried over Na2SO4 and concentrated to get the residue. The residue was purified by preparative HPLC to afford 62 mg (47% yield) of 2′-Hydroxy-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 98.83%. 1H NMR (DMSO-d6): δ 9.6 (s, 1H), 8.64-8.5 (bs, 1H), 7.92-7.72 (m, 4H), 7.72-7.5 (m, 4H), 7.26-7.12 (d, 1H), 7.24-7.16 (t, 1H), 7.0-6.84 (m, 2H), 4.24-4.06 (bd, 2H), 3.82-3.52 (m, 4H), 3.52-3.42 (bs, 2H), 3.24-3.02 (bd, 2H).

Workup

  1. customprepared by the method
  2. stirringThe reaction mixture was then stirred
  3. temperatureat reflux temperature for 3 hrs
  4. filtrationThe mixture was filtered over a bed of celite
  5. washThe celite was washed with MeOH
  6. concentrationthe filtrate was concentrated
  7. dissolutionThe residue was dissolved in EtOAc
  8. washwashed with 5% aqueous NaOH solution
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated
  11. customto get the residue
  12. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-1b74f30187184720a887e818dec5f78c
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

Loading…