Tetrahydrofuran → (R)-2-Methyl-propane-2-sulfinic acid [(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2,2,difluoro-3-hydroxy-1,3-dimethyl-butyl]-amide

HRID 1752460Notes

Reaction equation

HRID 1752460 reaction equation
[CH3:1][Mg]Cl.C(OC(=O)[C:8]([F:27])([F:26])[C@@:9]([C:18]1[C:23]([F:24])=[CH:22][CH:21]=[C:20]([Br:25])[N:19]=1)([NH:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH3:10])C.[CH2:29]1[CH2:33][O:32]CC1>>[Br:25][C:20]1[N:19]=[C:18]([C@:9]([NH:11][S@@:12]([C:14]([CH3:16])([CH3:15])[CH3:17])=[O:13])([CH3:10])[C:8]([F:26])([F:27])[C:33]([OH:32])([CH3:29])[CH3:1])[C:23]([F:24])=[CH:22][CH:21]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 86689142(R)-3-(6-Bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl esterHCID 178418332HCID 178418332, compound

Product 1

HCID 86689145(R)-2-Methyl-propane-2-sulfinic acid [(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2,2,difluoro-3-hydroxy-1,3-dimethyl-butyl]-amideYield 59.9%

Procedure

To methylmagnesium chloride 3M in THF (38.3 ml, 115 mmol) was added a solution of (R)-3-(6-bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl ester (5.12 g, 11.5 mmol, example 1e)) in THF (102 ml) at rt. After 2 hr stirring the reaction was quenched with addition of an aqueous ammonium chloride solution. The mixture was diluted with ethyl acetate and washed with water and brine, dried over sodium sulfate, filtered and evaporated. The crude product (4.78 g) was chromatographed over silica gel (cyclohexane/ethyl acetate 6:4) to give the title compound as a colourless solid. 2.97 g (59.9% yield).

Workup

  1. customwas quenched with addition of an aqueous ammonium chloride solution
  2. additionThe mixture was diluted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product (4.78 g) was chromatographed over silica gel (cyclohexane/ethyl acetate 6:4)

Sources & evidence

ORD record
ord-3ec7750b5b764fe0a7b86bf8058d138b
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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