Acrivastine → HCID 10360541, compound

HRID 542502

Reaction equation

HRID 542502 reaction equation
[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

Participants

3

Reactant 1

HCID 5284514Acrivastine

Product 1

HCID 10360541HCID 10360541, compound

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

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°.

Workup

  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

Sources & evidence

ORD record
ord-8ce2272845cd4c67afe1d10432f4ba1b
Source dataset
uspto-grants-1987_04
Patent number
US04657918

Linked notes

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