2,2-Difluoropropionic acid → 2-(1,1-Difluoroethyl)-5-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole

HRID 1013161Notes

Reaction equation

HRID 1013161 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])=[N:5][N:4]=[C:3]1[C:17]12[CH2:24][CH2:23][C:20]([C:25]([NH:27][NH2:28])=[O:26])([CH2:21][CH2:22]1)[CH2:19][CH2:18]2.[F:29][C:30]([F:35])([CH3:34])[C:31](O)=O>C(Cl)Cl>[F:29][C:30]([C:34]1[O:26][C:25]([C:20]23[CH2:23][CH2:24][C:17]([C:3]4[N:2]([CH3:1])[C:6]([C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=5[C:13]([F:15])([F:14])[F:16])=[N:5][N:4]=4)([CH2:18][CH2:19]2)[CH2:22][CH2:21]3)=[N:27][N:28]=1)([F:35])[CH3:31]

Participants

4

Reactant 2

HCID 27828252,2-Difluoropropionic acidHCID 592555674-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carbohydrazide

Product 1

HCID 160503652-(1,1-Difluoroethyl)-5-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carbohydrazide (4-A) (334 mg, 0.850 mmol) and 2,2-difluoropropionic acid (78 mg, 0.708 mmol) was suspended in methylene chloride, and DMC (1.2 g, 7.08 mmol) was added as solid. The mixture was stirred at room temperature under nitrogen for 48 hours before it was diluted with methylene chloride, washed with water, saturated sodium bicarbonate and brine. The crude product was purified by column chromatography to give 4-B as a white solid. MS (ESI+)=468.3 (M+1); 1H NMR (500 MHz, CDCl3): δ 2.15-2.33 (15H, m), 3.52 (3H, s), 7.61 (1H, m), 7.72 (2H, m), 7.85 (1H, m) ppm.

Workup

  1. additionDMC (1.2 g, 7.08 mmol) was added as solid
  2. washwashed with water, saturated sodium bicarbonate and brine
  3. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-44ad6d21945e47b798424d8d3432a0b8
Source dataset
uspto-grants-2011_07
Patent number
US07981910B2

Reaction notes

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