Ammonium formate → Ethyl 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate

HRID 2381116ノート

反応式

HRID 2381116 の反応式
[F:1][C:2]([F:31])([F:30])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH:10]=[CH:11][C:6]2=[N:5][N:4]=1.[CH:32]([O-])=O.[NH4+]>[Pd].C(O)C>[F:31][C:2]([F:1])([F:30])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([O:26][CH2:27][CH3:32])=[O:25])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH2:10][CH2:11][C:6]2=[N:5][N:4]=1

参加物

5

反応物 2

HCID 2723923Ammonium formate2 回HCID 67342348Methyl 2-[4-[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate

生成物 1

HCID 68503106Ethyl 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate収率 72.2%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 702Ethanol溶媒

実験手順

10% Palladium on carbon (0.536 g, 0.50 mmol) was added to methyl 2-[4-[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate (1.096 g, 2.52 mmol) and ammonium formate (1.587 g, 25.17 mmol) in ethanol (50 mL). The resulting mixture was stirred at 78° C., with further portions of ammonium formate being added every 5 hours until the reaction was complete. The reaction mixture was cooled to room temperature and the catalyst was removed by filtration. The filtrate was evaporated to dryness, redissolved in DCM (100 mL) and the solution was washed with water (50 mL) followed by brine (50 mL), then the solvents were evaporated to give crude product. The crude product was purified by flash silica chromatography, eluting with a gradient of 50 to 80% EtOAc in isohexane. Pure fractions were evaporated to afford ethyl 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate (0.820 g, 72.2%) as a gum.

後処理

  1. additionadded every 5 hours until the reaction
  2. customthe catalyst was removed by filtration
  3. customThe filtrate was evaporated to dryness
  4. dissolutionredissolved in DCM (100 mL)
  5. washthe solution was washed with water (50 mL)
  6. customthe solvents were evaporated
  7. customto give crude product
  8. customThe crude product was purified by flash silica chromatography
  9. washeluting with a gradient of 50 to 80% EtOAc in isohexane
  10. customPure fractions were evaporated

出典と根拠

ORDレコード
ord-db9a4031de0b4fccb73dd55d8cce5bd7
出典データセット
uspto-grants-2012_09
特許番号
US08258140B2

反応ノート

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