Sodium borohydride → Methyl (3rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate

HRID 394713

반응식

HRID 394713 반응식
[BH4-].[Na+].O[N:4]=[C:5]([C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([O:40][CH3:41])[CH:38]=2)[N:33]=[CH:32][C:31]=1[F:42])[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[CH2:10][CH:9]1[CH2:25][C:26]([O:28][CH3:29])=[O:27]>CO.[Mo](=O)(=O)=O>[NH2:4][CH:5]([C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([O:40][CH3:41])[CH:38]=2)[N:33]=[CH:32][C:31]=1[F:42])[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[CH2:10][CH:9]1[CH2:25][C:26]([O:28][CH3:29])=[O:27]

참가 물질

5

반응물 2

HCID 4311764Sodium borohydride2회HCID 136397852methyl (3RS,4RS)-4-[3-hydroxyimino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate

생성물 1

HCID 131724013Methyl (3rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate수율 51.8%

시약·촉매·용매 2

HCID 14802Molybdenum trioxide촉매2회HCID 887Methanol용매

반응 조건

온도
-2 °C

실험 절차

0.261 g of sodium borohydride was added, in several portions, to a mixture of 0.4 g of methyl (3RS,4RS)-4-[3-hydroxyimino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate in 25-cm3 of methanol cooled in the region of −2° C., with stirring and under an inert atmosphere. The reaction mixture was stirred in the region of 0° C. for 20 minutes and then 0.14 g of molybdenum trioxide wereadded. The reaction mixture was stirred in the region of 20° C. for 24 hours and then it was cooled in the vicinity of −2° C. and 0.261 g of sodium borohydride and 0.14 g of molybdenum trioxide were again added. The reaction mixture was stirred for 18 hours in the region of 20° C. and then filtered on celite. 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 μm; diameter 3 cm), eluting with a successive mixture of cyclohexane-ethyl acetate (50/50 by volume) and then dichloromethane-methanol (90/10 by volume) and collecting 10-cm3 fractions. Fractions 26 to 41 were combined and then concentrated to dryness according to the conditions described above. 0.202 g of methyl (3RS,4RS)-4-[3-(R,S)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate were obtained in the form of a colorless oil.

후처리

  1. stirringThe reaction mixture was stirred in the region of 0° C. for 20 minutes
  2. stirringThe reaction mixture was stirred in the region of 20° C. for 24 hours
  3. additionwere again added
  4. stirringThe reaction mixture was stirred for 18 hours in the region of 20° C.
  5. filtrationfiltered on celite
  6. concentrationThe filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  7. customThe evaporation residue was purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a successive mixture of cyclohexane-ethyl acetate (50/50 by volume)
  9. customdichloromethane-methanol (90/10 by volume) and collecting 10-cm3 fractions
  10. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-4dc26a9214a64a9f8a2477beee35107c
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06602884B2

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