Triethylamine → HCID 86656665, compound

HRID 888304Notes

Reaction equation

HRID 888304 reaction equation
[F:1][C:2]1[C:3]([C:22]2([OH:28])[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[N:4][N:5]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1.ClC(Cl)(O[C:33](=[O:39])OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.Cl.[CH3:49][NH:50][OH:51]>O1CCCC1>[F:1][C:2]1[C:3]([C:22]2([OH:28])[CH2:23][CH2:24][N:25]([C:33](=[O:39])[N:50]([OH:51])[CH3:49])[CH2:26][CH2:27]2)=[N:4][N:5]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 77906N-methylhydroxylamine hydrochlorideHCID 94429TriphosgeneHCID 67296333HCID 67296333, compound

Product 1

HCID 86656665HCID 86656665, compoundYield 172.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-fluoro-1-(4-methoxyphenyl)-5-(4-tolyl)-1H-pyrazol-3-yl)-4-piperidinol (3.61 g, 9.46 mmol) in tetrahydrofuran (946 mL), triphosgene (1.12 g, 3.78 mmol) and triethylamine (1.65 mL, 11.8 mmol) were added at 0° C., and the obtained solution was stirred at the same temperature for 40 minutes. To the reaction solution, N-methylhydroxylamine hydrochloride (988 mg, 11.8 mmol) and triethylamine (3.43 mL, 24.6 mmol) were added, and the obtained mixture was stirred at 80° C. for 3 hours. The reaction solution was cooled to room temperature, and distilled water was added to the reaction solution. The resulting solution was extracted with ethyl acetate. The organic layer was washed with 1 M hydrochloric acid, saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by recrystallization (n-hexane/ethyl acetate, 80° C.) to obtain the title compound (2.96 g, 6.51 mmol, 68%) as a pale yellow solid.

Workup

  1. stirringthe obtained mixture was stirred at 80° C. for 3 hours
  2. distillationdistilled water
  3. additionwas added to the reaction solution
  4. extractionThe resulting solution was extracted with ethyl acetate
  5. washThe organic layer was washed with 1 M hydrochloric acid, saturated sodium bicarbonate solution and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by recrystallization (n-hexane/ethyl acetate, 80° C.)

Sources & evidence

ORD record
ord-6e54c092cc6a43bf9e917d47a6c358eb
Source dataset
uspto-grants-2012_08
Patent number
US08247569B2

Reaction notes

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