Potassium hydroxy sulfite → (R)-5-(5-bromo-2-fluoro-phenyl)-4-(2,4-dimethoxy-benzyl)-5-methyl-1,1-dioxo-1lambda6-thiomorpholin-3-one

HRID 920156Notes

Reaction equation

HRID 920156 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C@@:8]2([CH3:26])[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=3[O:23][CH3:24])[C:12](=[O:25])[CH2:11]S[CH2:9]2)[CH:7]=1.O[O:29][S:30]([O-:32])=O.[K+]>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C@@:8]2([CH3:26])[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=3[O:23][CH3:24])[C:12](=[O:25])[CH2:11][S:30](=[O:32])(=[O:29])[CH2:9]2)[CH:7]=1

Participants

4

Reactant 2

HCID 23707502Potassium hydroxy sulfiteHCID 90016345(R)-5-(5-bromo-2-fluorophenyl)-4-(2,4-dimethoxybenzyl)-5-methylthiomorpholin-3-one

Product 1

HCID 90067087(R)-5-(5-bromo-2-fluoro-phenyl)-4-(2,4-dimethoxy-benzyl)-5-methyl-1,1-dioxo-1lambda6-thiomorpholin-3-oneYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (R)-5-(5-bromo-2-fluorophenyl)-4-(2,4-dimethoxybenzyl)-5-methylthiomorpholin-3-one (2.95 g, 6.49 mmol, Eq: 1.00) in methanol (100 ml) was added at 23° C. Oxone® (7.98 g, 13.0 mmol, Eq: 2.00). The reaction mixture was stirred at 23° C. for 16 hours. The reaction mixture was carefully quenched by addition of water at 0° C., then 10 ml of a diluted NaHSO3-solution, sat. NaHCO3-solution and ethyl acetate were added. Vigorous stirring was continued for 10 min. The organic layer was separated and washed with water, then dried over Na2SO4, filtered and evaporated to give a yellow oil which was chromatographed on 20 g silica gel with 0-50% ethyl acetate in heptane to give (R)-5-(5-bromo-2-fluoro-phenyl)-4-(2,4-dimethoxy-benzyl)-5-methyl-1,1-dioxo-1λ6-thiomorpholin-3-one (3 g, 6.17 mmol, 95.0% yield) as a white foam. MS (ISP): m/z=486.2 [M+H]+ and 488.1 [M+2+H]+.

Workup

  1. customThe reaction mixture was carefully quenched by addition of water at 0° C.
  2. addition10 ml of a diluted NaHSO3-solution, sat. NaHCO3-solution and ethyl acetate were added
  3. stirringVigorous stirring
  4. waitwas continued for 10 min
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give a yellow oil which
  11. customwas chromatographed on 20 g silica gel with 0-50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-d6045364a194485bb373245e1c9e07a1
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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