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

반응식

HRID 132917 반응식
[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]

참가 물질

5

반응물 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

생성물 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 ester수율 15%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
75 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a2963f1dd434468284faee0df6032b35
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388011B2

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