2-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide → HCID 69932798, compound

HRID 540787Notes

Reaction equation

HRID 540787 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:12]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][C:17]([CH:20]([O:23][CH3:24])[O:21][CH3:22])=[CH:16][CH:15]=3)[N:10]([CH2:25][CH3:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:27][C:28]([S:31]([N:33]=[C:34]1[CH2:37][O:36][CH2:35]1)=[O:32])([CH3:30])[CH3:29]>C1COCC1>[CH3:22][O:21][CH:20]([O:23][CH3:24])[C:17]1[CH:18]=[CH:19][C:14]([O:13][C:11]2[N:10]([CH2:25][CH3:26])[N:9]=[C:8]([C:4]3[CH:3]=[C:2]([C:34]4([NH:33][S:31]([C:28]([CH3:30])([CH3:29])[CH3:27])=[O:32])[CH2:37][O:36][CH2:35]4)[CH:7]=[CH:6][CH:5]=3)[CH:12]=2)=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 468399952-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamideHCID 67110835HCID 67110835, compound

Product 1

HCID 69932798HCID 69932798, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-Butylllithium in hexanes (2.5M, 3.83 mL, 9.59 mmol, 2.0 equiv) was added dropwise to a solution of 3-(3-bromophenyl)-5-[4-(dimethoxymethyl)phenoxy]-1-ethyl-1H pyrazole (2.0 g, 4.79 mmol, 1.0 equiv) in THF (32 mL) at −78° C. To this mixture was added dropwise a solution of 2-methyl-N-oxetane-3-ylidenepropane-2-sulfinamide (0.840 g, 4.79 mmol, 1.0 equiv, Example 95, Step 4) in 5 mL THF. The reaction mixture was stirred at −78° C. for 10 minutes and the cooling bath was removed. 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 dried over magnesium sulfate. The dried solution was filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (0-100% ethyl acetate:hexanes then flushing with 10% methanol/dichloromethane) to afford N-[3-{3-{5-[4-(dimethoxymethyl)phenoxy]-1-ethyl-1H-pyrazol-3-yl}phenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (2.17 g, 4.22 mmol, 88% yield). Calc'd (M+1)+501.23. Found: 468.1. Found mass is aldehyde formed from deprotection of acetal on LCMS.

Workup

  1. customthe cooling bath was removed
  2. additionSaturated aqueous ammonium chloride solution was added
  3. customthe crude product was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe dried solution was filtered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by flash chromatography on silica gel (0-100% ethyl acetate
  9. customhexanes then flushing with 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-994198fab9534fdaa1649e43ac823970
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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