Potassium Hydroxide → 5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide

HRID 1028494Notes

Reaction equation

HRID 1028494 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[C:11]([C:20]#[N:21])=[CH:12][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:15]=2)[CH:9]=1)([CH3:3])[CH3:2].[OH-:24].[K+]>O.CC(O)C>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[C:11]([C:20]([NH2:21])=[O:24])=[CH:12][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:14][CH:15]=2)[CH:9]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 533636455'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carbonitrile

Product 1

HCID 667165875'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

A solution of 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carbonitrile (727 mg, 2.28 mmol) and KOH (767 mg, 13.7 mmol) in H2O (7.70 mL) and i-PrOH (11.55 mL) was subjected to microwave irradiation (300 W 130° C., 4 h) in a sealed tube. The reaction mixture was concentrated in vacuo to remove the i-PrOH. The aqueous slurry obtained was diluted with water (50 mL) and extracted with EtOAc (50 mL). The organic extract was dried (Na2SO4) and concentrated in vacuo to afford 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide. The aqueous layer was acidified with concentrated HCl and extracted with EtOAc (3×50 mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo to give 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxylic acid as a colorless solid. 1H NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H), 7.04 (s, 1H), 6.77 (d, J=8.1, 1H), 3.68 (s, 3H), 2.84 (septet, J=6.7 Hz, 1H), 1.19 (d, J=6.7 Hz, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto remove the i-PrOH
  3. customThe aqueous slurry obtained
  4. extractionextracted with EtOAc (50 mL)
  5. extractionThe organic extract
  6. dry with materialwas dried (Na2SO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-084bfb6627e54b8880cbce5c19073e27
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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