Triethylamine → 2-[({4-[2-(Trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)amino]benzoic acid

HRID 874695Notes

Reaction equation

HRID 874695 reaction equation
[N:1]([C:4]1[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=1[C:6]([O:8]C)=[O:7])=[C:2]=[O:3].Cl.[F:15][C:16]([F:30])([F:29])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(N(CC)CC)C>O1CCCC1>[F:30][C:16]([F:15])([F:29])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH:23]1[CH2:24][CH2:25][N:26]([C:2]([NH:1][C:4]2[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=2[C:6]([OH:8])=[O:7])=[O:3])[CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 519494Methyl 2-isocyanatobenzoateHCID 219369704-[2-(Trifluoromethyl)phenyl]piperidine hydrochloride

Product 1

HCID 251382952-[({4-[2-(Trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)amino]benzoic acidYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 2-isocyanatobenzoate (10.00 g, 56.4 mmol) in tetrahydrofuran (30 ml) was slowly added to a solution of 4-(2-(trifluoromethyl)phenyl)piperidine hydrochloride (14.3 g, 53.8 mmol, Sigma) and triethylamine 99% (8.99 ml, 64.5 mmol) in tetrahydrofuran (120 ml) at 0° C. The mixture was removed from the cooling bath and stirred at room temperature for 15 min, at which time LC/MS analysis indicated that the reaction was complete. EtOH (75 ml) and aqueous LiOH (2N, 95 ml) were then added, and the solution was stirred for 6 h at room temperature. Subsequently, aqueous HCl (2N, 150 ml) was added, and the resulting mixture was extracted with EtOAc (2×600 ml). The EtOAc extract was dried over MgSO4 and concentrated to an off-white solid. Recrystallization from EtOAc yielded 14.0 g (66%) of 2-(4-(2-(trifluoromethyl)phenyl)piperidine-1-carboxamido) benzoic acid as a white solid, which was homogeneous by analytical high-performance liquid chromatography (>99%).

Workup

  1. customThe mixture was removed from the cooling bath
  2. additionEtOH (75 ml) and aqueous LiOH (2N, 95 ml) were then added
  3. stirringthe solution was stirred for 6 h at room temperature
  4. additionSubsequently, aqueous HCl (2N, 150 ml) was added
  5. extractionthe resulting mixture was extracted with EtOAc (2×600 ml)
  6. extractionThe EtOAc extract
  7. dry with materialwas dried over MgSO4
  8. concentrationconcentrated to an off-white solid
  9. customRecrystallization from EtOAc

Sources & evidence

ORD record
ord-249c0a2466194ec7bcfca384ab8a8243
Source dataset
uspto-grants-2015_03
Patent number
US08980924B2

Reaction notes

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