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

HRID 1514680ノート

反応式

HRID 1514680 の反応式
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

参加物

6

反応物 4

HCID 1140TolueneHCID 6363Isopropylamine2 回HCID 16682925Trimethylaluminum2 回HCID 667181316-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

生成物 1

HCID 469285696-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-isopropyl-nicotinamide収率 39.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
85 °C

実験手順

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]+.

後処理

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

出典と根拠

ORDレコード
ord-8ed9264300be45d6933d2ef5c550b426
出典データセット
uspto-grants-2012_07
特許番号
US08222246B2

反応ノート

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