Methyl Acrylate → 1-(2-Methoxycarbonyl-ethyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 132917

反応式

HRID 132917 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][CH3:32])(=[O:30])[CH:28]=[CH2:29].C(O[Na])(C)(C)C>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:29][CH2:28][C:27]([O:31][CH3:32])=[O:30])[N:15]=[C:16]([C:17]3[CH:18]=[CH:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:22]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 7294Methyl AcrylateHCID 684638853-(4-Trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl esterHCID 178418730sodium 2-methylpropan-2-olate

生成物 1

HCID 684627001-(2-Methoxycarbonyl-ethyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester収率 15%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
75 °C

実験手順

3-(4-Trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.85 g, 5.04 mmol) and methyl acrylate (0.50 mL, 5.6 mmol) were combined in toluene (30 mL) and heated to 75° C. The resulting mixture was treated with t-BuONa (100 mg), and heating continued for 48 h. The mixture was allowed to cool and partitioned between EtOAc (300 mL) and NaHCO3 (75 mL). The aqueous layer was extracted with EtOAc (3×75 mL). The combined extracts were dried over Na2SO4 and concentrated. Column chromatography (silica, 30-60% EtOAc/hexanes) afforded 343 mg (15%) of the title compound. TLC (silica, 50% EtOAc/hexanes): Rf=0.4. MS (electrospray): m/z calculated for C22H27F3N3O4 [M++H]454.20, found 454.1. 1H NMR (CDCl3, 400 MHz): 7.75 (br d, J=8.1 Hz, 2H), 7.64 (br s, 2H), 4.63 (br s, 2H), 4.30 (t, J=6.6 Hz, 2H), 3.75 (br s, 2H), 3.68 (s, 3H), 2.98 (t, J=6.6 Hz, 2H), 2.79 (br t, J=5.6 Hz, 2H), 1.48 (s, 9H).

後処理

  1. temperatureheating
  2. temperatureto cool
  3. custompartitioned between EtOAc (300 mL) and NaHCO3 (75 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (3×75 mL)
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-a2963f1dd434468284faee0df6032b35
出典データセット
uspto-grants-2008_06
特許番号
US07388011B2

関連ノート

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