Trimethylaluminum → HCID 86728101, compound

HRID 627628Notes

Reaction equation

HRID 627628 reaction equation
[CH3:1][S:2]([C:5]1([C:9]#[N:10])[CH2:8][CH2:7][CH2:6]1)(=[O:4])=[O:3].C([Li])CCC.[Br:16][C:17]1[CH:18]=[C:19](/[C:24](=[N:26]/[S@@:27]([C:29]([CH3:32])([CH3:31])[CH3:30])=[O:28])/[CH3:25])[C:20]([F:23])=[N:21][CH:22]=1.C[Al](C)C>C1COCC1.C1(C)C=CC=CC=1>[Br:16][C:17]1[CH:18]=[C:19]([C@:24]([NH:26][S:27]([C:29]([CH3:30])([CH3:32])[CH3:31])=[O:28])([CH3:25])[CH2:1][S:2]([C:5]2([C:9]#[N:10])[CH2:8][CH2:7][CH2:6]2)(=[O:4])=[O:3])[C:20]([F:23])=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 16682925TrimethylaluminumHCID 62474180HCID 62474180, compoundHCID 90301285HCID 90301285, compoundHCID 178418339Butyllithium

Product 1

HCID 86728101HCID 86728101, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(methylsulfonyl)cyclobutanecarbonitrile (8 g, 50.4 mmol) in THF (50 mL) was brought to −78° C. followed by the dropwise addition of butyllithium solution, 2.5M in hexanes (20.17 mL, 50.4 mmol). The resulting mixture was stirred at this temperature for 20 min. A solution of (R,E)-N-(1-(5-bromo-2-fluoropyridin-3-yl)ethylidene)-2-methylpropane-2-sulfinamide (9.0 g, 28.02 mmol) in toluene (40 mL) at −78° C. was treated with trimethylaluminum solution, 2.0 M in toluene (14 ml, 28.02 mmol) for 10 min. This solution was added dropwise to the previous mixture containing the nitrile and the resulting mixture was stirred at −78° C. for 1 h. The mixture was quenched with saturated NH4Cl and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-100% EtOAc/hexanes to afford an off-white solid as N—((R)-2-(5-bromo-2-fluoropyridin-3-yl)-1-((1-cyanocyclobutyl)sulfonyl)propan-2-yl)-2-methylpropane-2-sulfinamide (7.07 g, 14.72 mmol, 59.1% yield). LC/MS (ESI+) m/z=479.8 (M+H).

Workup

  1. customwas brought to −78° C.
  2. additionThis solution was added dropwise to the previous mixture
  3. stirringthe resulting mixture was stirred at −78° C. for 1 h
  4. customThe mixture was quenched with saturated NH4Cl
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed on silica gel using 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-aa465e068d8344f5ad0cfd7e02c5b5c2
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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