Water → 1-(3-Fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-1-yl)ethanone

HRID 1961530Notes

Reaction equation

HRID 1961530 reaction equation
[F:1][C:2]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH2:16][C:15]([C:21]4[CH:26]=[C:25]([Cl:27])[C:24]([Cl:28])=[C:23]([Cl:29])[CH:22]=4)([C:17]([F:20])([F:19])[F:18])[O:14][N:13]=3)=[CH:8][CH:7]=2)[CH2:5][NH:4][CH2:3]1.N1C=CC=CC=1.[C:36](Cl)(=[O:38])[CH3:37].O>C(Cl)Cl>[F:1][C:2]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH2:16][C:15]([C:21]4[CH:26]=[C:25]([Cl:27])[C:24]([Cl:28])=[C:23]([Cl:29])[CH:22]=4)([C:17]([F:19])([F:20])[F:18])[O:14][N:13]=3)=[CH:8][CH:7]=2)[CH2:3][N:4]([C:36](=[O:38])[CH3:37])[CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 6367Acetyl chlorideHCID 781477423-(4-(3-Fluoroazetidin-3-yl)phenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole

Product 1

HCID 566502931-(3-Fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-1-yl)ethanoneYield 87.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(4-(3-fluoroazetidin-3-yl)phenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 9, 94 mg) in 2 mL CH2Cl2 was added pyridine (0.05 mL) followed by acetyl chloride (31 mg). The reaction was allowed to stir at room temperature for 1 hour. Water (3 mL) was added. The reaction was diluted with 3 mL of CH2Cl2, stirred for 30 minutes and poured through a phase extractor. The CH2Cl2 layer was collected and concentrated. The crude product from the reaction was adsorbed onto silica and chromatographed on a 12 g silica column eluting with a gradient of 50% EtOAc/hexanes to 100% EtOAc/hexanes to yield 90 mg of the desired compound as a white foam. 1H NMR (CDCl3) δ 7.76 (d, 2H). 7.67 (s, 2H), 7.56 (d, 2H), 4.71-4.31 (m, 4H), 4.12 (d, 1H), 3.72 (d, 1H), 2.01 (s, 3H). LC/MS retention time=3.591 minutes; MS calculated for (C21H15Cl3F4N2O2), 509.714; found 511 M+H.

Workup

  1. stirringstirred for 30 minutes
  2. additionpoured through a phase extractor
  3. customThe CH2Cl2 layer was collected
  4. concentrationconcentrated
  5. customchromatographed on a 12 g silica column
  6. washeluting with a gradient of 50% EtOAc/hexanes to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-d6eef79e90624d8ab99453c6bb03b1db
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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