Phenylacetylene → 1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-[4-(5-phenyl-3-isoxazolyl)-2-thiazolyl]piperidine

HRID 1528519Notes

Reaction equation

HRID 1528519 reaction equation
[OH:1][N:2]=[CH:3][C:4]1[N:5]=[C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:27])[CH2:16][N:17]3[C:21]([CH3:22])=[CH:20][C:19]([C:23]([F:26])([F:25])[F:24])=[N:18]3)[CH2:11][CH2:10]2)[S:7][CH:8]=1.[C:28]1([C:34]#[CH:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Cl[O-].[Na+]>O1CCCC1>[CH3:22][C:21]1[N:17]([CH2:16][C:15]([N:12]2[CH2:13][CH2:14][CH:9]([C:6]3[S:7][CH:8]=[C:4]([C:3]4[CH:35]=[C:34]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[O:1][N:2]=4)[N:5]=3)[CH2:10][CH2:11]2)=[O:27])[N:18]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:20]=1

Participants

5

Reactant 3

HCID 10821PhenylacetyleneHCID 23665760Sodium HypochloriteHCID 866312434-[4-[(hydroxyimino)methyl]-2-thiazolyl]-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine2×

Product 1

HCID 687422261-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-[4-(5-phenyl-3-isoxazolyl)-2-thiazolyl]piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-[4-[(Hydroxyimino)methyl]-2-thiazolyl]-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine (i.e. the product of Example 2, Step C) (0.2 g, 0.5 mmol) was suspended in tetrahydrofuran (20 mL), and phenylacetylene (1.1 mL, 1 mmol) was added, followed by a slow dropwise addition of Clorox® bleach solution (6.15 wt. % sodium hypochlorite, 10 mL) over 1 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×0 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to give an oil, which was purified by flash column chromatography on silica gel using 10% methanol in ethyl acetate as eluant to give 70 mg of the title product, a compound of present invention, as a clear yellow oil.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×0 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customto give an oil, which
  8. customwas purified by flash column chromatography on silica gel using 10% methanol in ethyl acetate as eluant

Sources & evidence

ORD record
ord-badbb46b334a4f7ca47c0e27632affcd
Source dataset
uspto-grants-2015_07
Patent number
US09090604B2

Reaction notes

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