Trifluoroacetic acid → N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-propionamide

HRID 2045948Notes

Reaction equation

HRID 2045948 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:22]([F:25])([F:24])[F:23])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([CH:19]=O)=[C:16]([CH3:21])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:26]([NH2:30])(=[O:29])[CH2:27][CH3:28].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C1(C)C=CC=CC=1>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:22]([F:24])([F:25])[F:23])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([CH2:19][NH:30][C:26](=[O:29])[CH2:27][CH3:28])=[C:16]([CH3:21])[CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6578PropionamideHCID 12052TriethylsilaneHCID 866812905-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carbaldehyde

Product 1

HCID 54766756N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-propionamideYield 49.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carbaldehyde (120 mg), propionamide (66 mg), trifluoroacetic acid (68 μl) and triethylsilane (144 μl) in toluene (2 ml) is refluxed overnight. After 20 hours the reaction mixture is concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-propionamide (68 mg, compound 1.5 in Table 1) as a white foam. MS (HPLC/MS): 465 (MH+). Retention time: 1.98 min.

Workup

  1. temperatureis refluxed overnight
  2. concentrationAfter 20 hours the reaction mixture is concentrated in vacuo
  3. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-5abc48d08e24450d9c6f8678318f67b6
Source dataset
uspto-grants-2013_11
Patent number
US08592418B2

Reaction notes

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