Sodium borohydride → Methyl (3rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate

HRID 394709

반응식

HRID 394709 반응식
[BH4-].[Na+].O[N:4]=[C:5]([C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][C:28]=1[F:39])[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:16][C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)[CH2:10][CH:9]1[CH2:22][C:23]([O:25][CH3:26])=[O:24]>CO.[Mo](=O)(=O)=O>[NH2:4][CH:5]([C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][C:28]=1[F:39])[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:16][C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)[CH2:10][CH:9]1[CH2:22][C:23]([O:25][CH3:26])=[O:24]

참가 물질

5

반응물 2

HCID 4311764Sodium borohydride2회HCID 137178928Methyl (3RS,4RS)-4-[3-hydroxyimino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl)-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate

생성물 1

HCID 131724009Methyl (3rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate수율 37.2%

시약·촉매·용매 2

HCID 14802Molybdenum trioxide촉매2회HCID 887Methanol용매

반응 조건

온도
-5 °C

실험 절차

0.695 g of sodium borohydride was added in several portions to a mixture of 0.98 g of methyl (3RS,4RS)-4-[3-hydroxyimino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate in 50-cm3 of methanol cooled to the region of −5° C., with stirring and under inert atmosphere. The reaction was very exothermic and in the vicinity of 0° C., 0.365 g of molybdenum trioxide were added all at once. The reaction mixture was stirred in the region of 20° C. for 20 hours and then it was cooled to the vicinity of −6° C. and 0.695 g of sodium borohydride and 0.365 g of molybdenum trioxide were again added. The reaction mixture was stirred for 5 hours in the region of 20° C. and was then filtered on celite and the insoluble matter was washed twice with 50-cm3 of methanol. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 m; diameter 3 cm; height 25 cm), eluting with a successive mixture of cyclohexane-ethyl acetate (50/50 by volume), ethyl acetate and then dichloromethane-methanol (90/10 by volume) and collecting 50-cm3 fractions. Fractions 17 to 20 were combined and then concentrated to dryness according to the conditions described above. 0.355 g of methyl (3RS,4RS)-4-[3-(R,S)amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate were obtained in the form of a colorless oil.

후처리

  1. additionwere added all at once
  2. stirringThe reaction mixture was stirred in the region of 20° C. for 20 hours
  3. additionwere again added
  4. stirringThe reaction mixture was stirred for 5 hours in the region of 20° C.
  5. filtrationwas then filtered on celite
  6. washthe insoluble matter was washed twice with 50-cm3 of methanol
  7. concentrationThe filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  8. customThe evaporation residue was purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 m; diameter 3 cm; height 25 cm), eluting with a successive mixture of cyclohexane-ethyl acetate (50/50 by volume), ethyl acetate
  10. customdichloromethane-methanol (90/10 by volume) and collecting 50-cm3 fractions
  11. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-3725dd827f1a4ee98b446ae7e3c27bb3
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06602884B2

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