Water → N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide

HRID 1374171Notes

Reaction equation

HRID 1374171 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:16])[C:5](/[CH:8]=[N:9]/[S:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])=[N:6][CH:7]=1.[CH3:17][Mg]Cl.O>C(Cl)Cl.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[C:4]([F:16])[C:5]([C@H:8]([NH:9][S:10]([C:12]([CH3:13])([CH3:15])[CH3:14])=[O:11])[CH3:17])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 21075886(NE)-N-[(5-bromo-3-fluoro-2-pyridinyl)methylidene]-2-methylpropane-2-sulfinamideHCID 178418332HCID 178418332, compound2×

Product 1

HCID 68520381N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of N-[(1E)-(5-bromo-3-fluoropyridin-2-yl)methylidene]-2-methyl-propane-2-sulfinamide (18.63 g, 60.65 mmol) in CH2Cl2 (375 mL) was cooled to −50° C. under N2. Methylmagnesium chloride (3M in THF, 30.32 mL, 90.97 mmol) was added dropwise, the reaction was stirred for 1 h. Additional methylmagnesium chloride (5.0 mL, 15.0 mmol) was added after 30 minutes to drive the reaction to completion. Water (200 mL) and brine (200 mL) were added, and the reaction allowed to warm to room temperature. The aqueous layer was extracted 4× with CH2Cl2, and the combined organics were dried over Na2SO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 10–40% ethyl acetate in hexanes to provide N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 325.0 for M+H+(81Br).

Workup

  1. customthe reaction to completion
  2. extractionThe aqueous layer was extracted 4× with CH2Cl2
  3. dry with materialthe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. washeluted with 10–40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8320446cd91b4b588732422f102cca0f
Source dataset
uspto-grants-2007_01
Patent number
US07163951B2

Reaction notes

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