Toluene → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-isopropyl-nicotinamide

HRID 1514680Notes

Reaction equation

C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].CO[C:11](=[O:34])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[N:22][O:23][C:24]=2[CH2:25][OH:26])=[N:14][CH:13]=1.C1(C)C=CC=CC=1>O1CCOCC1>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C:21]2[C:20]([CH2:19][O:18][C:15]3[CH:16]=[CH:17][C:12]([C:11]([NH:8][CH:5]([CH3:7])[CH3:6])=[O:34])=[CH:13][N:14]=3)=[C:24]([CH2:25][OH:26])[O:23][N:22]=2)=[CH:28][CH:29]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A trimethylaluminium solution (2 M in toluene, 418 μL, 0.84 mmol) was added to a solution of isopropylamine (49.6 mg, 0.84 mmol) in dioxane (3.75 mL). 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (75.0 mg, 0.21 mmol) in dioxane (3.75 mL) was added after 1 h at 50° C. The reaction mixture was stirred at 85° C. overnight. Again trimethylaluminium solution in toluene (2 M, 418 μL, 0.84 mmol) and isopropylamine (49.6 mg, 0.84 mmol) was added and stirring was continued for 3 h at 85° C. The solvent was removed by distillation. The residue was purified by chromatography (silica, ethyl acetate:heptane=1:1 to 7:3) to afford the title compound (32 mg, 39%) as white solid. MS: m/e=386.2 [M+H]+.

Workup

stirringstirring
waitwas continued for 3 h at 85° C
customThe solvent was removed by distillation
customThe residue was purified by chromatography (silica, ethyl acetate:heptane=1:1 to 7:3)

Sources & evidence

ORD record: ord-8ed9264300be45d6933d2ef5c550b426
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222246B2

Reaction notes

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