Acrivastine → (E)-3-(6-(3-(Pyrrolidin-1-yl)-1-(p-tolyl)prop-1-en-1-yl)pyridin-2-yl)propanoic Acid

HRID 638644

반응식

HRID 638644 반응식
[N:1]1([CH2:6]/[CH:7]=[C:8](/[C:16]2[N:21]=[C:20](/[CH:22]=[CH:23]/[C:24]([OH:26])=[O:25])[CH:19]=[CH:18][CH:17]=2)\[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1>[Ni]>[N:1]1([CH2:6]/[CH:7]=[C:8](/[C:16]2[N:21]=[C:20]([CH2:22][CH2:23][C:24]([OH:26])=[O:25])[CH:19]=[CH:18][CH:17]=2)\[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

3

반응물 1

HCID 5284514Acrivastine

생성물 1

HCID 10360541(E)-3-(6-(3-(Pyrrolidin-1-yl)-1-(p-tolyl)prop-1-en-1-yl)pyridin-2-yl)propanoic Acid

시약·촉매·용매 1

HCID 935Nickel촉매

실험 절차

A solution of compound 2, vide supra, (3 g) in alcohol (100 mL) containing Raney nickel (1 g) was stirred under hydrogen at room temperature and pressure until the calculated quantity of hydrogen had been absorbed (ca. 45 minutes). The reduced ester was recovered by filtration and evaporation and purified by column chromatography on silica gel using petroleum ether as eluent. Butyllithium (10 mL, 1.64M in hexane) was added under nitrogen to a stirred suspension of triphenyl-2-pyrrolidinoethylphosphonium bromide (7.2 g) in dry toluene (75 mL) to prepare a Wittig reagent. Treatment of this ester with Wittig reagent by the method of Example 1 followed by saponification gave a mixture of two isomeric acids which were separated by fractional crystallization from ethyl acetate/petroleum ether mixtures. The less soluble E isomer, 3-{6-[3-Pyrrolidino-1-(4-tolyl)prop-1E-enyl]-2-pyridyl}-propionic acid (Compound B), melted at 156°-157°.

후처리

  1. custompressure until the calculated quantity of hydrogen had been absorbed (ca. 45 minutes)
  2. filtrationThe reduced ester was recovered by filtration and evaporation
  3. custompurified by column chromatography on silica gel
  4. additionButyllithium (10 mL, 1.64M in hexane) was added under nitrogen to a stirred suspension of triphenyl-2-pyrrolidinoethylphosphonium bromide (7.2 g) in dry toluene (75 mL)
  5. customto prepare a Wittig reagent
  6. customgave
  7. additiona mixture of two isomeric acids which
  8. customwere separated by fractional crystallization from ethyl acetate/petroleum ether

출처 및 근거

ORD 기록
ord-1e77d5c1660f48519e3ba0a12c4898fd
출처 데이터셋
uspto-grants-1985_12
특허 번호
US04562258

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