Water → HCID 178458446, compound

HRID 1172693Notes

Reaction equation

HRID 1172693 reaction equation
[F:1][CH:2]([F:32])[O:3][C:4]1[CH:11]=[C:10]([O:12][CH:13]([C:16]2[S:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=3)=[N:18][C:17]=2[CH3:31])[CH2:14][CH3:15])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7].C(N(CC)CC)C.Cl.[NH2:41][OH:42].O>CO>[F:32][CH:2]([F:1])[O:3][C:4]1[CH:11]=[C:10]([O:12][CH:13]([C:16]2[S:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=3)=[N:18][C:17]=2[CH3:31])[CH2:14][CH3:15])[CH:9]=[CH:8][C:5]=1[C:6]([NH:41][OH:42])=[NH:7]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 595563432-Difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile

Product 1

HCID 178458446HCID 178458446, compoundYield 61.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 485 mg of 2-difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile in 10 mL of methanol was added 4.166 mL of triethylamine followed by 316 mg of hydroxylamine hydrochloride. The resulting mixture was heated in a sealed tube to 140° C. under microwave irradiation for 30 minutes. After allowing it to cool down to room temperature, the mixture was poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 60/ethyl acetate 40) to give 320 mg of 2-difluoromethoxy-N-hydroxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzamidine.

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 60/ethyl acetate 40)

Sources & evidence

ORD record
ord-8249ff4bf0db42a59884776e99be8fa6
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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