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

HRID 68570Notes

Reaction equation

HRID 68570 reaction equation
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].[Cl:6][C:7]1[CH:8]=[C:9]([C:14]2([C:27]([F:30])([F:29])[F:28])[O:18][N:17]=[C:16]([C:19]3[S:23][C:22]([CH3:24])=[C:21]([CH2:25][NH2:26])[CH:20]=3)[CH2:15]2)[CH:10]=[C:11]([Cl:13])[CH:12]=1.CCN(C(C)C)C(C)C>ClCCl>[Cl:6][C:7]1[CH:8]=[C:9]([C:14]2([C:27]([F:29])([F:28])[F:30])[O:18][N:17]=[C:16]([C:19]3[S:23][C:22]([CH3:24])=[C:21]([CH2:25][NH:26][C:1](=[O:4])[CH2:2][CH3:3])[CH:20]=3)[CH2:15]2)[CH:10]=[C:11]([Cl:13])[CH:12]=1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 68293128HCID 68293128, compound

Product 1

HCID 60168071N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Propionyl chloride (0.17 ml) is added to a solution of C-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-yl}-methylamine (816 mg) and DIPEA (1 ml) in dichloromethane (10 ml) at room temperature. After 3 hours at RT, the reaction is quenched with water. The aqueous phase is separated and further extracted two times with dichloromethane. The organic phases are combined, dried over MgSO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC and by crystallization in a diethylether/petroleum ether mixture to yield N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide (compound 1.6, 122 mg) as white crystals. MS (HPLC/MS): 465 (MH+). Retention time: 1.96 min.

Workup

  1. customthe reaction is quenched with water
  2. customThe aqueous phase is separated
  3. extractionfurther extracted two times with dichloromethane
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC and by crystallization in a diethylether/petroleum ether mixture

Sources & evidence

ORD record
ord-4b8fe2d99d3740c58e75446a94f455ed
Source dataset
uspto-grants-2014_09
Patent number
US08822466B2

Reaction notes

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