반응 #481884

ord-31642637ea1c4fb78ce594543e904eae

반응 조건

온도
60°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도After cooling to about 20° C.
  2. 2
    기타The organic phase was separated
  3. 3
    세척washed 5 times with 100 cm3 of water
  4. 4
    건조with 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate
  5. 5
    여과filtered
  6. 6
    농축concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  7. 7
    기타The evaporation residue obtained
  8. 8
    기타was purified by chromatography, under a nitrogen pressure of 50 kPa
  9. 9
    세척on a column of silica gel (particle size 20-45 μ; diameter 2 cm; height 40 cm), eluting with a cyclohexane-ethyl acetate (68/32 by volume) mixture
  10. 10
    기타15-cm3 fractions were collected
  11. 11
    농축Fractions 15 to 21 were concentrated

실험 절차

A suspension composed of 0.95 g of methyl (3RS,4RS) and (3SR,4RS)-4-[3-(3-fluoro-6-methoxy-quinolin-4-yl)propyl]piperidine-3-acetate, 0.7 g of potassium carbonate, 0.68 g of 2-(2-bromoethylthio)-thiophene in 40 cm3 of dimethylformamide was stirred for 16 hours at a temperature in the region of 60° C. under an inert atmosphere. After cooling to about 20° C., the reaction mixture was poured over 200 cm3 of water and 200 cm3 of ethyl acetate. The organic phase was separated after settling out and then washed 5 times with 100 cm3 of water and then with 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue obtained was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ; diameter 2 cm; height 40 cm), eluting with a cyclohexane-ethyl acetate (68/32 by volume) mixture. 15-cm3 fractions were collected. Fractions 15 to 21 were concentrated. 480 mg of methyl (3RS,4RS)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(thien-2-yl)thioethyl]piperidine-3-acetate were obtained in the form of an orange-colored oil.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06602884B2uspto-grants-2003_08