2,6-Lutidine → 2-Cyclopropyl-7-fluoro-6-formyl-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17461

Reaction equation

HRID 17461 reaction equation
[CH:1]1([C:4]2[O:5][C:6]3[C:12]([F:13])=[C:11]([CH:14]=C)[C:10]([CH3:16])=[CH:9][C:7]=3[N:8]=2)[CH2:3][CH2:2]1.[N:17]1[C:22](C)=CC=CC=1C.I([O-])(=O)(=O)=[O:26].[Na+].S([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.[Cl-].[Na+].O.[Os](=O)(=O)(=O)=O.C(OCC)(=O)C>[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:22]#[N:17])[C:10]([CH3:16])=[C:11]([CH:14]=[O:26])[C:12]=3[F:13])[N:8]=2)[CH2:2][CH2:3]1

Participants

10

Reactant 4

HCID 79372,6-LutidineHCID 24437Sodium SulfiteHCID 23667635Sodium periodateHCID 866308512-Cyclopropyl-7-fluoro-5-methyl-6-vinyl-1,3-benzoxazole

Product 1

HCID 860975112-Cyclopropyl-7-fluoro-6-formyl-5-methyl-1,3-benzoxazole-4-carbonitrileYield 86%

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

2-Cyclopropyl-7-fluoro-5-methyl-6-vinyl-1,3-benzoxazole-4-(carbonitrile (I-180) (500 mg, 2.06 mmol) was dissolved in 1,4-dioxane (7.5 ml) and water (2.5 ml), then at room temperature, 2,6-lutidine (481 μl, 4.13 mmol), a catalytic amount of osmium tetroxide and sodium metaperiodate (1.766 g, 8.26 mmol) were added. After stirring at the same temperature for 13 hours, sodium sulfite (purity 90%, 1.61 g, 12.38 mmol) and water (5 ml) were added. The solution was fractionated with ethyl acetate and saturated brine. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=6:1) to obtain the entitled compound (435 mg, 86%) as a white solid.

Workup

  1. extractionThe aqueous layer was further extracted twice with ethyl acetate
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe insoluble matter was separated by filtration
  5. customthe solvent was evaporated away under reduced pressure
  6. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-5c3ed14dd65e4ffbb63d2e8cd43f4d2e
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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