Water → HCID 57489433, compound

HRID 1961534Notes

Reaction equation

HRID 1961534 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:28])([F:27])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4([F:24])[CH2:23][NH:22][CH2:21]4)=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N(CC)CC)C.[CH:36]1([C:39](Cl)=[O:40])[CH2:38][CH2:37]1.O>C(Cl)Cl>[CH:36]1([C:39]([N:22]2[CH2:23][C:20]([C:17]3[CH:18]=[CH:19][C:14]([C:11]4[CH2:10][C:9]([C:4]5[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=5)([C:25]([F:27])([F:26])[F:28])[O:13][N:12]=4)=[CH:15][CH:16]=3)([F:24])[CH2:21]2)=[O:40])[CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 58079827HCID 58079827, compound

Product 1

HCID 57489433HCID 57489433, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the 5-(3,5-dichlorophenyl)-3-(4-(3-fluoroazetidin-3-yl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 15, 65 mg) in 2 mL CH2Cl2 was added triethyl amine (50 μL) followed by cyclopropane carbonyl chloride (19 mg). The reaction was allowed to stir at room temperature for 30 minutes. Water (5 mL) was added. The reaction was diluted with an additional 5 mL of CH2Cl2, stirred for 5 minutes at room temp then passed through a phase separation tube. The CH2Cl2 layer was collected and condensed. The crude material was adsorbed on silica and chromatographed on a 12 g silica column, eluting with a gradient of 0% to 100% ethyl acetate in heptane. Fractions containing the desired material were combined and concentrated. Et2O (˜½ mL) was added to the resulting film. Placing the flask on high vacuum overnight resulted in formation of a white foam. Yield 67 mg (98%) of the desired product. 1H NMR (CDCl3) δ ppm 7.76 (d, 2H), 7.63-7.51 (s, 4H), 7.45 (s, 1H), 4.8-4.7 (m, 1H), 4.6-4.3 (m, 3H), 4.12 (d, 1H), 3.74 (d, 1H), 1.6-1.4 (m, 1H), 1.07 (m, 2H), 0.86 (m, 2H). LC/MS retention time=3.654 minutes, MS calculated for (C23H18Cl2F4N2O2), 500.07; found 501.0 M+H.

Workup

  1. stirringstirred for 5 minutes at room temp
  2. customthen passed through a phase separation tube
  3. customThe CH2Cl2 layer was collected
  4. customcondensed
  5. customchromatographed on a 12 g silica column
  6. washeluting with a gradient of 0% to 100% ethyl acetate in heptane
  7. additionFractions containing the desired material
  8. concentrationconcentrated
  9. additionEt2O (˜½ mL) was added to the resulting film
  10. customon high vacuum overnight
  11. customresulted in formation of a white foam

Sources & evidence

ORD record
ord-91310cbdb094472b9a69cef4d11863e1
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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