Trifluoroacetic acid → HCID 10004097, compound

HRID 1452674Notes

Reaction equation

HRID 1452674 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([NH:21][C:22](=[O:40])[CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]4[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[CH:33]=4)=[CH:27][CH:26]=3)[CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[F:39][C:34]1[CH:33]=[C:32]([CH:37]=[CH:36][C:35]=1[F:38])[O:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][CH2:23][C:22]([NH:21][C:16]2[CH:15]=[C:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH:19]=[CH:18][C:17]=2[F:20])=[O:40])=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57526924HCID 57526924, compound

Product 1

HCID 10004097HCID 10004097, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a solution of tert-butyl-4-[3-({3-[4-(3,4-difluorophenoxy)phenyl]propanoyl}amino)-4-fluorophenyl]-1-piperidinecarboxylate (85.0 mg, 0.150 mmol) in CH2Cl2 (2.0 mL) was added trifluoroacetic acid (170 mg, 1.50 mmol) at room temperature. The reaction mixture was stirred for 10 min and concentrated in vacuo. The residue was dissolved in CHCl3/i-PrOH (3:1, 10 mL) and was basified to pH 11 with 5% KOH solution. The organic layer was extracted and the aqueous layer was extracted with CHCl3/i-PrOH (3:1, 3×10 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to afford 3-[4-(3,4-difluorophenoxy)phenyl]-N-[2-fluoro-5-(4-piperidinyl)phenyl]propanamide (65.0 mg, 92%): 1H NMR (400 MHz, CD3OD) δ 8.27-8.12 (m, 1H), 7.39 (s, 1H), 7.33-7.17 (m, 2H), 7.17-7.06 (m, 1H), 7.06-6.97 (m, 1H), 6.97-6.87 (m, 3H), 6.86-6.74 (m, 1H), 6.74-6.62 (m, 1H), 6.15-5.63 (br, 1H), 3.55-3.31 (m, 2H), 3.15-2.97 (m, 2H), 2.97-2.79 (m, 2H), 2.79-2.59 (m, 3H), 2.05-1.79 (m, 4H); ESMS m/e: 455.2 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in CHCl3/i-PrOH (3:1, 10 mL)
  3. extractionThe organic layer was extracted
  4. extractionthe aqueous layer was extracted with CHCl3/i-PrOH (3:1, 3×10 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0d4b94dff0004ae58583d9d455abc59c
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

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