Hydrochloric Acid → (4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylcarbamoyl)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid

HRID 76086Notes

Reaction equation

HRID 76086 reaction equation
C[O:2][C:3](=[O:36])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23](=[O:35])[NH:24][C:25]4[CH:26]=[N:27][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:30]=4)=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.Cl>C1COCC1.O.[OH-].[Li+]>[F:34][C:31]([F:32])([F:33])[C:28]1[N:27]=[CH:26][C:25]([NH:24][C:23]([C:20]2[CH:21]=[CH:22][C:17]([C:14]3[CH:15]=[CH:16][C:11]([CH:8]4[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:36])=[O:2])[CH2:10][CH2:9]4)=[CH:12][CH:13]=3)=[N:18][CH:19]=2)=[O:35])=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66615765(4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylcarbamoyl)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester

Product 1

HCID 24936888(4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylcarbamoyl)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid

Reagents, catalysts & solvents 2

HCID 3939Lithium HydroxideSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To 60 mg (0.1 mmol), (4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylcarbamoyl)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester in THF/H2O (10 mL; 4:1), 5 mL (4M) aqueous Lithium Hydroxide solution was added and the mixture stirred at 60° C. for 5 hours. Acidified with concentrated hydrochloric acid which precipitated the desired compound. Filtered and dried under vacuum to afford (4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylcarbamoyl)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid, which was subsequently dissolved in methanol (5 mL) one equivalent of potassium hydroxide and 2 mL of H2O were added and the resulting mixture was stirred at 40 C for 2 hours. Evaporated to dryness to afford (4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylcarbamoyl)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid as the potassium salt: M+1=484.1. HRMS=484.1822. 1H NMR (400 MHz, MeOD) δ ppm 0.79 (d, J=7.33 Hz, 1H) 1.11 (td, J=12.44, 2.91 Hz, 3H) 1.43-1.55 (m, 2H) 1.67-1.78 (m, J=7.14, 7.14, 6.95, 6.57 Hz, 2H) 1.79-1.89 (m, 3H) 2.02 (d, J=7.33 Hz, 2H) 2.14 (t, J=7.33 Hz, 1H) 2.47 (s, 1H) 7.29 (d, J=8.34 Hz, 2H) 7.75 (d, J=8.59 Hz, 1H) 7.88-7.95 (m, 2H) 8.31 (dd, J=8.46, 2.40 Hz, 1H) 8.43 (dd, J=8.46, 2.15 Hz, 1H) 8.97 (d, J=2.27 Hz, 1H) 9.08 (d, J=1.52 Hz, 1H)

Workup

  1. customprecipitated the desired compound
  2. filtrationFiltered
  3. customdried under vacuum

Sources & evidence

ORD record
ord-9263fc1e476d4288bcaa9003629edc9b
Source dataset
uspto-grants-2014_09
Patent number
US08835451B2

Reaction notes

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