Water → HCID 178513355, compound

HRID 2263433Notes

Reaction equation

HRID 2263433 reaction equation
[F:1][CH:2]([F:40])[O:3][C:4]1[CH:11]=[C:10]([O:12][CH2:13][C:14]2[S:18][C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:16][C:15]=2[CH2:29][N:30]2[CH2:35][CH2:34][CH:33]([C:36]([F:39])([F:38])[F:37])[CH2:32][CH2:31]2)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7].C(N(CC)CC)C.Cl.[NH2:49][OH:50].O>CO>[F:40][CH:2]([F:1])[O:3][C:4]1[CH:11]=[C:10]([O:12][CH2:13][C:14]2[S:18][C:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:23][CH:24]=3)=[N:16][C:15]=2[CH2:29][N:30]2[CH2:31][CH2:32][CH:33]([C:36]([F:39])([F:38])[F:37])[CH2:34][CH2:35]2)[CH:9]=[CH:8][C:5]=1[C:6]([NH:49][OH:50])=[NH:7]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 59594780HCID 59594780, compound

Product 1

HCID 178513355HCID 178513355, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 830 mg of 2-difluoromethoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrile in 13 mL of methanol was added 5.7 mL of triethylamine followed by 430 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 480 mg of 2-difluoromethoxy-N-hydroxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-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-1f939c524a654e7bb54f2620dfe1ffaa
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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