2-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide → N-[3-(3-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}phenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide

HRID 540775Notes

Reaction equation

HRID 540775 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([C:13]2[CH:17]=[C:16]([O:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[N:15]([CH2:29][CH3:30])[N:14]=2)[CH:10]=[CH:11][CH:12]=1.[CH3:31][C:32]([S:35]([N:37]=[C:38]1[CH2:41][O:40][CH2:39]1)=[O:36])([CH3:34])[CH3:33]>O1CCCC1>[CH2:29]([N:15]1[C:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)=[CH:17][C:13]([C:9]2[CH:8]=[C:7]([C:38]3([NH:37][S:35]([C:32]([CH3:34])([CH3:33])[CH3:31])=[O:36])[CH2:41][O:40][CH2:39]3)[CH:12]=[CH:11][CH:10]=2)=[N:14]1)[CH3:30]

Participants

5

Reactant 3

HCID 468399952-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamideHCID 67111295(3-bromophenyl)-1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazoleHCID 178418339Butyllithium

Product 1

HCID 69933066N-[3-(3-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}phenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamideYield 82.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium in hexanes (2.50 M, 1.3 mL, 3.2 mmol, 1.5 equiv) was added to a solution of -(3-bromophenyl)-1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazole (1.32 g, 3.21 mmol, 1.5 equiv) in tetrahydrofuran (18 mL) at −78° C. The reaction mixture was stirred at −78° C. for 20 minutes, and then a solution of 2-methyl-N-oxetan-3-ylidenepropane-2-sulfinamide (375 mg, 2.14 mmol, 1 equiv) in tetrahydrofuran (2 mL) was added via syringe. The reaction mixture was stirred at −78° C. for 5 minutes, then the cooling bath was removed. After stirring for an additional 15 minutes, saturated aqueous ammonium chloride solution was added, and the crude product was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, and the washed solution was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated. The residue was purified by flash-column chromatography (10% ethyl acetate-hexanes, grading to 100% ethyl acetate, then flushing with 10% methanol-dichloromethane) to afford N-[3-(3-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}phenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (894 mg, 82%). Calc'd (M+1)+: 508.2. Found: 507.9.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 5 minutes
  2. customthe cooling bath was removed
  3. stirringAfter stirring for an additional 15 minutes
  4. additionsaturated aqueous ammonium chloride solution was added
  5. customthe crude product was partitioned between ethyl acetate and water
  6. washThe organic layer was washed with saturated aqueous sodium chloride solution
  7. dry with materialthe washed solution was dried over sodium sulfate
  8. filtrationThe dried solution was filtered
  9. concentrationthe filtrate was concentrated
  10. customThe residue was purified by flash-column chromatography (10% ethyl acetate-hexanes
  11. customflushing with 10% methanol-dichloromethane)

Sources & evidence

ORD record
ord-da31e9f913804954bf0f05d1dbae639a
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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