Hydrochloric Acid → (NE,R)-N-[[5-[(2-fluorophenyl)methoxy]-2-pyridinyl]methylidene]-2-methylpropane-2-sulfinamide

HRID 511825Notes

Reaction equation

HRID 511825 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]#[N:13])=[N:10][CH:11]=1.CC(C[AlH]CC(C)C)C.Cl.C(=O)(O)[O-].[Na+].[CH3:33][C:34]([S@:37](N)=[O:38])([CH3:36])[CH3:35]>ClCCl.S([O-])([O-])(=O)=O.[Cu+2].CO>[F:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9](/[CH:12]=[N:13]/[S@@:37]([C:34]([CH3:36])([CH3:35])[CH3:33])=[O:38])=[N:10][CH:11]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14487Diisobutylaluminum hydrideHCID 516892Sodium BicarbonateHCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 67290985HCID 67290985, compound

Product 1

HCID 87457872(NE,R)-N-[[5-[(2-fluorophenyl)methoxy]-2-pyridinyl]methylidene]-2-methylpropane-2-sulfinamideYield 36%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of Reactant 5-(2-fluorobenzyloxy)picolinonitrile (690 mg, 3.0 mmol) in dichloromethane (20 mL) was added DIBAL-H (3.7 mL, 3.6 mmol, 0.99 M) at −78° C. After being stirred at −78° C. for 4 hours, methanol (2 mL) was added to the mixture. 1N hydrochloric acid (0.5 mL) was added to the mixture at room temperature. The mixture was stirred at room temperature for 1 hour. Sat. sodium bicarbonate aqueous solution was added to the mixture until the pH was neutrized. The organic layer was extracted with dichloromethane, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in dichloromethane (20 mL). Copper(II) sulfate (1.2 g, 7.6 mmol) followed by (R)-(+)-2-methyl-2-propanesulfinamide (370 mg, 3.0 mmol) were added to the mixture respectively and the mixture was stirred for overnight at room temperature. The reaction mixture was filtrated off through a pad of Celite and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (2:1 (v/v)) to give 360 mg (36% yield) of the title compound as a colorless oil:

Workup

  1. stirringThe mixture was stirred at room temperature for 1 hour
  2. extractionThe organic layer was extracted with dichloromethane
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  6. additionwere added to the mixture respectively
  7. stirringthe mixture was stirred for overnight at room temperature
  8. filtrationThe reaction mixture was filtrated off through a pad of Celite
  9. concentrationthe filtrate was concentrated in vacuo
  10. customThe residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (2:1 (v/v))

Sources & evidence

ORD record
ord-f07bac2f0bbe4f6ca873d9d81206f310
Source dataset
uspto-grants-2015_08
Patent number
US09101616B2

Reaction notes

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