Dichloroacetyl chloride → isopropyl 3-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)propanoate

HRID 1782197Notes

Reaction equation

HRID 1782197 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([NH:20][CH2:21][CH2:22][C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH:17]=[CH:16][N:15]=2)[O:11][N:10]=1.C(N(CC)CC)C.[Cl:36][CH:37]([Cl:41])[C:38](Cl)=[O:39]>ClCCl>[Cl:36][CH:37]([Cl:41])[C:38]([N:20]([CH2:21][CH2:22][C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]1[CH:17]=[CH:16][N:15]=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:3]3[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:13]=2)[CH:19]=1)=[O:39]

Participants

5

Reactant 3

HCID 6593Dichloroacetyl chlorideHCID 8471TriethylamineHCID 69055819HCID 69055819, compound

Product 1

HCID 69055938isopropyl 3-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)propanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isopropyl 3-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)propanoate (520 mg, 1.23 mmol) was dissolved in anhydrous dichloromethane (25 mL) with triethylamine (270 mg, 2.7 mmol). The mixture was cooled in an ice-bath under nitrogen, then a solution of dichloroacetyl chloride (320 mg, 2.17 mmol) was added dropwise. After the addition was completed the ice-bath was removed and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and then washed successively with water, 10% hydrochloric acid and saturated sodium bicarbonate solution. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with 95:5 hexanes:ethyl acetate to yield isopropyl 3-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)propanoate (Cpd. No. 57). 1H NMR (CDCl3): 8.38 (m, 1H), 8.01 (s, 1H), 7.80 (m, 1H), 7.50-7.41 (m, 4H), 7.18 (s, 1H), 6.86 (s, 1H), 6.32 (s, 2H), 5.08 (m, 1H), 1.38 ppm (s, 6H).

Workup

  1. temperatureThe mixture was cooled in an ice-bath under nitrogen
  2. additionAfter the addition
  3. customwas removed
  4. additionThe reaction mixture was diluted with dichloromethane
  5. washwashed successively with water, 10% hydrochloric acid and saturated sodium bicarbonate solution
  6. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by flash column chromatography, on silica gel
  10. washeluting with 95:5 hexanes

Sources & evidence

ORD record
ord-517a6a3359654cc69758b385cdba65dd
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

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