Methylamine → 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-n-hydroxy-2,n'-dimethyl-benzamidine

HRID 471369Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([CH:18]=[N:19][OH:20])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl[N:29]1C(=O)CC[C:30]1=O.CN.C(N(CC)CC)C>CN(C=O)C.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:25])([F:27])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH:19][OH:20])=[N:29][CH3:30])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzaldehyde oxime (i.e. the product of Step 2, 500 mg) in DMF (25 mL) was added N-chloro succinimide (168 mg) and heated to 75° C. for 1 h. After cooling, the reaction mixture was poured onto water and extracted with MTBE. The combined organic layers were dried (Na2SO4) and concentrated in vacuo to ¼ of the original volume to obtain the crude hydroxamic acid chloride. This mixture was added to a solution of methylamine (0.66 mL, 41 mg) and triethylamine (0.18 mL, 0.13 g) in THF and stirred at room temperature over night. After concentration in vacuo, the mixture was purified by chromatography on silica gel to obtain the title compound (270 mg, 39%) as a colorless solid.

Workup

temperatureAfter cooling
additionthe reaction mixture was poured onto water
extractionextracted with MTBE
dry with materialThe combined organic layers were dried (Na2SO4)
concentrationconcentrated in vacuo
customto obtain the crude hydroxamic acid chloride
concentrationAfter concentration in vacuo
customthe mixture was purified by chromatography on silica gel

Sources & evidence

ORD record: ord-de7079c22e0d458b9e79585448c73ea2
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633134B2

Reaction notes

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