Methanol → 7-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylic acid methyl ester

HRID 536422Notes

Reaction equation

HRID 536422 reaction equation
C(N(CC)CC)C.[CH3:8][OH:9].Br[C:11]1[C:16]2=[N:17][S:18][N:19]=[C:15]2[C:14]([C:20]2[CH2:24][C:23]([C:29]3[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=3)([C:25]([F:28])([F:27])[F:26])[O:22][N:21]=2)=[CH:13][CH:12]=1.[C]=O.CN(C)[CH:41]=[O:42]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:8][O:9][C:41]([C:11]1[C:16]2=[N:17][S:18][N:19]=[C:15]2[C:14]([C:20]2[CH2:24][C:23]([C:29]3[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=3)([C:25]([F:28])([F:27])[F:26])[O:22][N:21]=2)=[CH:13][CH:12]=1)=[O:42]

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 584979314-Bromo-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazoleHCID 178418416HCID 178418416, compound

Product 1

HCID 584979897-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

Triethylamine (7.8 ml) and methanol (72 ml) were added at ambient temperature to a solution of 4-bromo-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole (7.96 g) (Example I6) in N,N-dimethylformamide (72 ml). [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (“PdCl2(dppf)”) (654 mg) was added and the reaction mixture was stirred in a pressure reactor in an atmosphere of carbon monoxide (3 bar) at 87° C. for 16 hours. The reaction mixture was cooled to ambient temperature, filtered through a plug of Celite® and concentrated. The residue was purified by column chromatography (heptane/ethyl acetate) to give 7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylic acid methyl ester (4.01 g) as an orange oil. 1H-NMR (CDCl3, 400 MHz): 8.43-7.57 (m, 5H), 4.66 (d, 1H), 4.27 (d, 1H), 4.09 (s, 3H) ppm.

Workup

  1. filtrationfiltered through a plug of Celite®
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-f96ae9f94dfe40e0aab451da03cf9c69
Source dataset
uspto-grants-2014_10
Patent number
US08859592B2

Reaction notes

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