Trifluoroacetic acid → Cyclopropanecarboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide

HRID 68582

Reaction equation

HRID 68582 reaction equation
[CH3:1][C:2]1[O:3][C:4]([C:9]2[CH2:13][C:12]([C:18]3[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=3)([C:14]([F:17])([F:16])[F:15])[O:11][N:10]=2)=[CH:5][C:6]=1[CH:7]=O.[CH:27]1([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C1(C)C=CC=CC=1>[CH3:1][C:2]1[O:3][C:4]([C:9]2[CH2:13][C:12]([C:18]3[CH:19]=[C:20]([Cl:26])[C:21]([Cl:25])=[C:22]([Cl:24])[CH:23]=3)([C:14]([F:16])([F:15])[F:17])[O:11][N:10]=2)=[CH:5][C:6]=1[CH2:7][NH:32][C:30]([CH:27]1[CH2:29][CH2:28]1)=[O:31]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 80376CyclopropanecarboxamideHCID 867066532-Methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-carbaldehyde

Product 1

HCID 86706657Cyclopropanecarboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amideYield 86.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-carbaldehyde (250 mg, Example 3, step I), cyclopropanecarboxylic acid amide (160 mg), trifluoroacetic acid (0.142 ml) and triethylsilane (0.301 ml) in toluene (4 ml) is refluxed overnight. After 23 hours the reaction mixture is concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield cyclopropanecarboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide (251 mg, compound 2.2 in Table 2) as a yellowish foam. MS (HPLC/MS): 495 (MH+). Retention time: 2.02 min.

Workup

  1. temperatureis refluxed overnight
  2. concentrationAfter 23 hours the reaction mixture is concentrated in vacuo
  3. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-856336fd4dcb41e88ef6010aff5220e1
Source dataset
uspto-grants-2014_09
Patent number
US08822466B2

Linked notes

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