Propionyl chloride → N-(1-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethyl)-propionamide

HRID 2045954Notes

Reaction equation

HRID 2045954 reaction equation
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].CCN(C(C)C)C(C)C.[Cl:15][C:16]1[CH:17]=[C:18]([C:23]2([C:37]([F:40])([F:39])[F:38])[O:27][N:26]=[C:25]([C:28]3[S:32][C:31]([CH:33]([NH2:35])[CH3:34])=[C:30]([CH3:36])[CH:29]=3)[CH2:24]2)[CH:19]=[C:20]([Cl:22])[CH:21]=1>ClCCl>[Cl:15][C:16]1[CH:17]=[C:18]([C:23]2([C:37]([F:39])([F:38])[F:40])[O:27][N:26]=[C:25]([C:28]3[S:32][C:31]([CH:33]([NH:35][C:1](=[O:4])[CH2:2][CH3:3])[CH3:34])=[C:30]([CH3:36])[CH:29]=3)[CH2:24]2)[CH:19]=[C:20]([Cl:22])[CH:21]=1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 665872941-{5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethylamine

Product 1

HCID 54766913N-(1-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethyl)-propionamideYield 30.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Propionyl chloride (20 mg) and Hünig base (70 μl) are added to a solution of 1-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethylamine (60 mg) in dichloromethane (1 ml). After 19 hours at room temperature, the reaction is quenched with water. The reaction mixture is extracted three times with dichloromethane. The combined organic phases are dried over MgSO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield N-(1-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-ethyl)-propionamide (21 mg, compound 1.49 in Table 1) as a light yellow oil. MS (HPLC/MS): 479 (MH+). Retention time: 2.01 min.

Workup

  1. customthe reaction is quenched with water
  2. extractionThe reaction mixture is extracted three times with dichloromethane
  3. dry with materialThe combined organic phases are dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-74bb86adb45049019768c0ba16cf96f9
Source dataset
uspto-grants-2013_11
Patent number
US08592418B2

Reaction notes

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