Tetrahydrofuran → HCID 67235388, compound

HRID 1186136Notes

Reaction equation

HRID 1186136 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@:8]([NH:18][S@@:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])([CH3:17])[C:9]([F:16])([F:15])C(OCC)=O)[CH:7]=1.[CH3:26][Mg]Br.[CH2:29]1[CH2:33][O:32]CC1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@@:8]([NH:18][S@@:19]([C:21]([CH3:24])([CH3:22])[CH3:23])=[O:20])([C:9]([F:16])([F:15])[C:33]([OH:32])([CH3:29])[CH3:26])[CH3:17])[CH:7]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 67234404HCID 67234404, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67235388HCID 67235388, compoundYield 99.7%

Conditions

Temperature
23 °C

Procedure

To a solution of (R)-ethyl 3-(5-bromo-2-fluorophenyl)-3-((R)-1,1-dimethylethylsulfinamido)-2,2-difluorobutanoate (intermediate A3C) (10.5 g, 23.6 mmol) in anhydrous THF (150 ml) at −78° C. was dropwise added a methylmagnesium bromide solution (3.2 M in 2-methyl-THF; 59.1 ml, 189 mmol), the cooling bath was removed and the mixture was stirred at 23° C. for 18 h. Poured cautiously into sat. NH4Cl-sol., extracted with ethyl acetate, washed organic layer with brine and dried over Na2SO4. Removal of the solvent in vacuum left the (R)-N-((R)-2-(5-bromo-2-fluorophenyl)-3,3-difluoro-4-hydroxy-4-methylpentan-2-yl)-2-methylpropane-2-sulfinamide (10.565 g, 23.6 mmol, 99.7% yield) as a yellow gum, which was used in the next step without further purification. MS (ISP): m/z=430.1 [(M+H)+] and 432.1 [(M+2+H)+].

Workup

  1. customthe cooling bath was removed
  2. additionPoured cautiously into sat. NH4Cl-sol
  3. extraction, extracted with ethyl acetate
  4. washwashed organic layer with brine
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent in vacuum

Sources & evidence

ORD record
ord-f44eaa250a4a4e428fe841f0fe928f79
Source dataset
uspto-grants-2014_03
Patent number
US08673894B2

Reaction notes

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