Tetrahydrofuran → 1-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid

HRID 631917Notes

Reaction equation

HRID 631917 reaction equation
C[O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4[N:21]=[N:22][N:23]([CH3:41])[C:24]=4[NH:25][C:26]([O:28][CH:29]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=4)[CH3:30])=[O:27])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].C1COCC1.[OH-].[Na+]>C(O)C>[CH3:41][N:23]1[C:24]([NH:25][C:26]([O:28][CH:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:39])[F:40])[CH:32]=2)[CH3:30])=[O:27])=[C:20]([C:17]2[CH:18]=[CH:19][C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4([C:3]([OH:4])=[O:2])[CH2:7][CH2:6]4)=[CH:13][CH:12]=3)=[CH:15][CH:16]=2)[N:21]=[N:22]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 1180627761-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester

Product 1

HCID 727046171-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acidYield 100.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-(4′-{1-Methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester (410 mg, 0.726 mmol) was dissolved 4 mL of THF and 4 mL of ethanol. To this stirred solution was added 1N sodium hydroxide solution (8 mL). The mixture was stirred at room temperature overnight. TLC indicated complete consumption of the starting material. The mixture was concentrated and the residue was dissolved in 15 mL of water. Dilute hydrochloric acid (1N, 9 mL) was added. The white solid was filtered and dried in the air to give 1-(4′-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid (400 mg, 100% yield). LC/MS calcd for C29H25F3N4O4 (m/e) 550.0, obsd 551.0 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.13-1.29 (m, 2.6H), 1.44-1.52 (m, 2H), 1.60 (br d, 2.4H), 3.86 (s, 3H), 5.75-5.95 (br m, 1H), 7.43 (d, J=8.1 Hz, 2.5H), 7.61 (d, J=8.1 Hz, 2.5H), 7.69 (br m, 3.5H), 7.79 (d, J=7.6 Hz, 3.5H), 9.65 and 10.05 (br s, 1H), 12.35 (s, 1H).

Workup

  1. customconsumption of the starting material
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in 15 mL of water
  4. additionDilute hydrochloric acid (1N, 9 mL) was added
  5. filtrationThe white solid was filtered
  6. customdried in the air

Sources & evidence

ORD record
ord-9e3810edc0c24208a16efd4b096d8417
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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