Toluene → tert-butyl (3R)-4-(5-fluoro-6-methylpyridin-2-yl)-3-methylpiperazine-1-carboxylate

HRID 69127ノート

反応式

HRID 69127 の反応式
Br[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][CH:3]=1.[CH3:10][C@H:11]1[NH:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.O>[F:9][C:5]1[CH:4]=[CH:3][C:2]([N:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][C@H:11]2[CH3:10])=[N:7][C:6]=1[CH3:8]

参加物

7

反応物 4

HCID 1140TolueneHCID 2756811(R)-1-Boc-3-methylpiperazineHCID 27831806-Bromo-3-fluoro-2-methylpyridineHCID 23676156Sodium t-butoxide

生成物 1

HCID 86694329tert-butyl (3R)-4-(5-fluoro-6-methylpyridin-2-yl)-3-methylpiperazine-1-carboxylate収率 95.8%

試薬・触媒・溶媒 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

To a mixture of 500 mg of 6-bromo-3-fluoro-2-methylpyridine, 580 mg of tert-butyl (3R)-3-methylpiperazine-1-carboxylate, 506 mg of sodium tert-butoxide, and 61 mg of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and 7.5 mL of toluene was added 48 mg of tris(dibenzylidenacetone)dipalladium (0), followed by stirring at 110° C. for 3 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to obtain 780 mg of tert-butyl (3R)-4-(5-fluoro-6-methylpyridin-2-yl)-3-methylpiperazine-1-carboxylate.

後処理

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-ea53b8ac4d754d359f1c144f130b2d37
出典データセット
uspto-grants-2014_09
特許番号
US08822448B2

反応ノート

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