Methyl morpholine oxide → N-[4-cyano-3-(trifluoromethyl)phenyl]-2,3-dihydroxy-2-methylpropanamide

HRID 457263Notes

Reaction equation

HRID 457263 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:14])[C:11]([CH3:13])=[CH2:12])=[CH:5][C:4]=1[C:15]([F:18])([F:17])[F:16])#[N:2].C[N+]1([O-])CC[O:23]CC1.OS([O-])=O.[Na+].[OH2:32].CC(C)=O>C(O)(C)(C)C.O.[Os](=O)(=O)(=O)=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:14])[C:11]([OH:23])([CH3:13])[CH2:12][OH:32])=[CH:5][C:4]=1[C:15]([F:17])([F:16])[F:18])#[N:2]

Participants

8

Reactant 4

HCID 82029Methyl morpholine oxide2×HCID 11149469N-[4-Cyano-3-(trifluoromethyl)phenyl]-2-methylprop-2-enamideHCID 18366337Propan-2-one--water (1/1)HCID 23665763Sodium Bisulfite

Product 1

HCID 9882395N-[4-cyano-3-(trifluoromethyl)phenyl]-2,3-dihydroxy-2-methylpropanamide

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalyst2×HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

In a 50 ml flask, equipped with a magnetic stirrer, 0.50 g of the compound (7) in 1.8 ml of tert-butyl alcohol was added to a mixture of 0.301 g of N-methylmorpholine-N-oxide (═NMO) (monohydrate) and 16 mg of osmium tetroxide in 15 ml of a water/acetone mixture (5:2). The reaction mixture was stirred at room temperature overnight. The conversion was ˜60%. Another 0.30 g of NMO (monohydrate) and 16 mg of osmium tetroxide were added and the reaction was followed with HPLC. Stirring was continued for 3.5 hours. The reaction was worked-up by addition of a slurry of 1.0 g NaHSO3 and 1.0 g of Celite in 40 ml of water. The Celite was removed by filtration, and the filtrate was neutralised to pH 7.0 with 1N aqueous H2SO4, and the acetone was removed at reduced pressure. The remaining solution was set to pH 2.0 with 1N aqueous H2SO4 and was extracted with 3×35 ml of ethyl acetate. The combined organic layers were washed with 35 ml of brine, dried (Na2SO4) and concentrated at reduced pressure. The crude product was purified by column chromatography (Merck 60 SiO2, eluens ethyl acetate) to give the purified (5C) as a slightly coloured oil, which solidified (off-white solid) after a few days. Isolated yield: 0.400 gram (70.5%). 1H-NMR confirmed the structure.

Workup

  1. customIn a 50 ml flask, equipped with a magnetic stirrer
  2. stirringStirring
  3. waitwas continued for 3.5 hours
  4. customThe Celite was removed by filtration
  5. customthe acetone was removed at reduced pressure
  6. extractionwas extracted with 3×35 ml of ethyl acetate
  7. washThe combined organic layers were washed with 35 ml of brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated at reduced pressure
  10. customThe crude product was purified by column chromatography (Merck 60 SiO2, eluens ethyl acetate)
  11. customto give the
  12. custompurified (5C) as a slightly coloured oil, which
  13. customafter a few days
  14. customIsolated yield: 0.400 gram (70.5%)

Sources & evidence

ORD record
ord-afa1d66bcd944d6faaadfdc30ee5c808
Source dataset
uspto-grants-2007_03
Patent number
US07186854B2

Reaction notes

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