Triethylamine → HCID 71529468, compound

HRID 1500068Notes

Reaction equation

HRID 1500068 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:23]([F:26])([F:25])[F:24])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:27](Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[S:40]1[CH2:43][CH:42]([CH2:44][NH2:45])[CH2:41]1>ClCCl.CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:23]([F:24])([F:25])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([NH:45][CH2:44][CH:42]4[CH2:43][S:40][CH2:41]4)=[O:19])=[C:21]([CH3:27])[CH:22]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 251573784-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]benzoic acidHCID 53488446HCID 53488446, compound

Product 1

HCID 71529468HCID 71529468, compoundYield 54.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a suspension of 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoic acid (836 mg, prepared as described for example in WO200/9080250) in dichloromethane (30 ml) was added oxalyl chloride (280 mg) and then one drop of N,N-dimethylformamide. The reaction mixture stirred at room temperature until the solids were dissolved, and the solvent was evaporated in vacuo to give a solid, which was dissolved in dichloromethane (10 ml) and the resulting solution added dropwise to a solution of triethylamine (0.5 ml) and thietan-3-ylmethanamine (example B, 250 mg) in dichloromethane (20 ml) at room temperature, under argon. The reaction was stirred overnight at room temperature, diluted with water, and the organic layer washed with 1N hydrochloric acid solution, then with 1N sodium hydroxide solution, then with brine. The organic phase dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by column chromatography (eluent heptane/ethyl acetate) afforded the title compound as a solid (570 mg). 1H-NMR (CDCl3, 400 MHz): 7.60-7.40 (m, 6H), 6.02 (m, 1H), 4.10 (d, 1H), 3.70 (d, 1H), 3.65 (t, 2H), 3.55 (m, 1H), 3.33 (t, 2H), 3.05 (dd, 2H), 2.50 (s, 3H).

Workup

  1. dissolutionwere dissolved
  2. customthe solvent was evaporated in vacuo
  3. customto give a solid, which
  4. stirringThe reaction was stirred overnight at room temperature
  5. washthe organic layer washed with 1N hydrochloric acid solution
  6. dry with materialThe organic phase dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (eluent heptane/ethyl acetate)

Sources & evidence

ORD record
ord-af69e1970e7a4f98a38f8967a00ea643
Source dataset
uspto-grants-2015_12
Patent number
US09204648B2

Reaction notes

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