Ethyl Acetate → 6-[3-(3,4-Difluoro-phenyl)-5-formyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

HRID 1514707Notes

Reaction equation

HRID 1514707 reaction equation
[CH3:1][O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([F:32])[CH:26]=3)=[N:14][O:15][C:16]=2/[CH:17]=C/C2C=CC=CC=2)=[N:6][CH:5]=1.I([O-])(=O)(=O)=[O:35].[Na+].C(OCC)(=O)C.CCCCCCC>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[CH3:1][O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([F:32])[CH:26]=3)=[N:14][O:15][C:16]=2[CH:17]=[O:35])=[N:6][CH:5]=1

Participants

9

Reactant 4

HCID 8857Ethyl Acetate2×HCID 8900HeptaneHCID 23667635Sodium periodateHCID 667182936-[3-(3,4-Difluoro-phenyl)-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 866462566-[3-(3,4-Difluoro-phenyl)-5-formyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl esterYield 61%

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

6-[3-(3,4-Difluoro-phenyl)-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (5.0 g, 11.2 mmol), osmium(VIII) oxide (70.9 mg, 0.28 mmol), sodium metaperiodate (9.54 mg, 44.6 mmol), benzyltriethylammonium chloride (1.04 mg, 4.46 mmol) in dioxane (75 mL) and water (25 mL) were heated for 15 min at 120° C. in a microwave. Addition of water and extraction with ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:4 to 1:1) afforded the title compound (2.54 g, 61%) as a white solid. MS: m/e=375.1 [M+H]+.

Sources & evidence

ORD record
ord-f011d43cf986416e94ce77beb88fbfa0
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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