Dichloromethane → tert-Butyl 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate

HRID 1257530ノート

反応式

HRID 1257530 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2[CH2:19][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[O:17][N:16]=2)[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br-].[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([Zn+])=[N:32][CH:33]=1.[K+].[K+].[K+].C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.ClCCl>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([C:2]2[CH:3]=[C:4]([CH:12]=[C:13]([C:15]3[CH2:19][C@@H:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[O:17][N:16]=3)[CH:14]=2)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[N:32][CH:33]=1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 62717Edetate TripotassiumHCID 58096179tert-butyl 3-bromo-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoateHCID 178427808HCID 178427808、化合物

生成物 1

HCID 66895837tert-Butyl 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate収率 90.4%

試薬・触媒・溶媒 2

HCID 178418851HCID 178418851、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °C

実験手順

To a solution of tert-butyl 3-bromo-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate (19.95 g, 49.5 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.76 g, 1.48 mmol) in dioxane (247 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 198 mL, 99 mmol). The reaction mixture was heated to 75° C. After 1 h, the reaction was cooled to ambient temperature. Aqueous ethylenediaminetetraacetic acid tripotassium salt (0.4 M, 200 mL) and dichloromethane (200 mL) were added. The mixture was stirred for 15 min and the organic solvent was evaporated. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% ethyl acetate 98% ethyl acetate/methanol) gave the title compound (18.6 g). MS 416.1 (M+1).

後処理

  1. temperaturethe reaction was cooled to ambient temperature
  2. customthe organic solvent was evaporated
  3. extractionThe mixture was extracted with dichloromethane (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% ethyl acetate 98% ethyl acetate/methanol)

出典と根拠

ORDレコード
ord-a0b70897865d482a814efc7fdc0b37bd
出典データセット
uspto-grants-2013_06
特許番号
US08461185B2

反応ノート

読み込み中…