Dichloroacetyl chloride → tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate

HRID 1782181Notes

Reaction equation

HRID 1782181 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:36])[CH:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:25]([CH3:27])[CH3:26])[CH:17]=[CH:16][N:15]=2)[O:11][N:10]=1.C(N(CC)CC)C.[Cl:44][CH:45]([Cl:49])[C:46](Cl)=[O:47]>C(Cl)Cl>[Cl:44][CH:45]([Cl:49])[C:46]([N:20]([CH2:21][CH2:22][C:23](=[O:36])[CH:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:25]([CH3:27])[CH3:26])[C:18]1[CH:17]=[CH:16][N:15]=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])[CH:13]=2)[CH:19]=1)=[O:47]

Participants

5

Reactant 3

HCID 6593Dichloroacetyl chlorideHCID 8471TriethylamineHCID 69060036tert-Butyl 6-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-2-methyl-4-oxohexan-3-ylcarbamate

Product 1

HCID 57588429tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamateYield 34.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

tert-Butyl 6-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-2-methyl-4-oxohexan-3-ylcarbamate (445 mg, 0.83 mmol) was dissolved in methylene chloride (10 mL) with triethylamine (140 μL, 1.0 mmol). The solution was cooled on an ice-water bath and then a solution of dichloroacetyl chloride (100 μL, 1.0 mmol) in methylene chloride (1 mL) was added dropwise. The reaction mixture was allowed to stir overnight while warming to room temperature. The solution was washed successively with water and saturated sodium bicarbonate solution, then 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 0.5:99.5 methanol:methylene chloride to provide tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate (185 mg) as a pink foam. 1H NMR (CDCl3): 8.85 (d, 1H), 7.91 (d, 1H), 7.61-7.35 (m, 5H), 7.18 (s, 1H), 6.11 (s, 1H), 5.02 (d, 1H), 4.28-4.08 (m, 2H), 3.15-2.82 (m, 3H), 2.20-2.10 (m, 1H), 1.42 (s, 9H), 1.08 (d, 3H), 0.85 ppm (d, 3H). MW=644 confirmed by LC-MS, tr=16.72 min (Method Y) MH+=642-646.

Workup

  1. temperatureThe solution was cooled on an ice-water bath
  2. washThe solution was washed successively with water and saturated sodium bicarbonate solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by flash column chromatography on silica gel
  7. washeluting with 0.5:99.5 methanol

Sources & evidence

ORD record
ord-1f354f5c808144c182616a7296bf1a62
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

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