4-Fluorobenzoyl chloride → 5-(4-Fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine

HRID 2369598ノート

反応式

HRID 2369598 の反応式
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[O:15]([CH2:22][C:23]1[CH:31]=[C:26]2[CH:27]=[N:28][CH2:29][CH2:30][N:25]2[N:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[CH:35][CH:34]=1>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([N:28]2[CH2:29][CH2:30][N:25]3[N:24]=[C:23]([CH2:22][O:15][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:31]=[C:26]3[CH2:27]2)=[O:38])=[CH:35][CH:34]=1

参加物

6

反応物 3

HCID 678794-Fluorobenzoyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 679583882-Phenoxymethyl-6,7-dihydro-pyrazolo[1,5-a]pyrazine

生成物 1

HCID 679583635-(4-Fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine収率 87.2%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 10340Sodium Carbonate溶媒

実験手順

Sodium triacetoxyborohydride (20.8 mg, 0.093 mmol) was added to a stirred solution of 2-phenoxymethyl-6,7-dihydro-pyrazolo[1,5-a]pyrazine (15 mg, 0.062 mmol) in DCM (0.5 mL). The mixture was stirred at room temperature for 16 hours and then, 4-fluorobenzoyl chloride (0.011 mL, 0.093 mmol) was added and the mixture stirred at room temperature for 1 hour. The mixture was diluted with a saturated solution of Na2CO3 and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield rac-(4-fluoro-phenyl)-(2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-methanone (19 mg, 84% yield) as a colourless oil that precipitated upon standing. 1H NMR (500 MHz, CDCl3) δ ppm 1.56 (d, J=6.9 Hz, 3H), 3.59 (br. s., 1H), 4.34 (br. s., 1H), 4.05-4.22 (m, 1H), 4.22-4.32 (m, 1H), 5.04 (s, 2H), 5.58 (br. s., 1H), 6.15 (br. s., 1H), 6.96 (t, J=7.4 Hz, 1H), 7.00 (d, J=7.8 Hz, 2H), 7.10-7.20 (m, 2H), 7.27-7.34 (m, 2H), 7.40-7.49 (m, 2H).

後処理

  1. stirringthe mixture stirred at room temperature for 1 hour
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

出典と根拠

ORDレコード
ord-9a62e3ca32984318b5280e679e9e864a
出典データセット
uspto-grants-2014_04
特許番号
US08703946B2

反応ノート

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