Sodium hydride → ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(6-cyano-1,2,3,4-tetrahydro-2-naphthyl)acrylate

HRID 1738697

반응식

HRID 1738697 반응식
C1(C)C=CC(S([O-])(=O)=O)=CC=1.[C:12]([C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[CH2:20][CH:19]([CH2:24][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:18][CH2:17]2)#[N:13].[H-].[Na+].[C:46]([O:50][C:51]([N:53]1[CH2:57][CH2:56][C@H:55]([O:58][C:59]2[CH:64]=[CH:63][C:62]([C:65](=O)[C:66]([O:68][CH2:69][CH3:70])=[O:67])=[CH:61][CH:60]=2)[CH2:54]1)=[O:52])([CH3:49])([CH3:48])[CH3:47]>O1CCCC1.C(OCC)(=O)C>[C:46]([O:50][C:51]([N:53]1[CH2:57][CH2:56][C@H:55]([O:58][C:59]2[CH:60]=[CH:61][C:62]([C:65](=[CH:24][CH:19]3[CH2:18][CH2:17][C:16]4[C:21](=[CH:22][CH:23]=[C:14]([C:12]#[N:13])[CH:15]=4)[CH2:20]3)[C:66]([O:68][CH2:69][CH3:70])=[O:67])=[CH:63][CH:64]=2)[CH2:54]1)=[O:52])([CH3:49])([CH3:48])[CH3:47]

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 10316641Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-2-oxoacetateHCID 21844271(6-Cyano-1,2,3,4-tetrahydro-2-naphthyl)methyltriphenylphosphonium p-toluenesulfonate

생성물 1

HCID 57296335ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(6-cyano-1,2,3,4-tetrahydro-2-naphthyl)acrylate수율 65.9%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

9.0 g of (6-cyano-1,2,3,4-tetrahydro-2-naphthyl)methyltriphenylphosphonium p-toluenesulfonate was suspended in 150 ml of tetrahydrofuran, followed by gradual addition of 600 mg of 60% sodium hydride. The thus prepared mixture was refluxed under heating for 20 minutes. After cooling down to room temperature, to the resulting reaction solution was added 10 ml of a tetrahydrofuran solution containing 4.16 g of ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-2-oxoacetate. The resulting reaction mixture was stirred for 10 minutes, and then refluxed under heating for 2 hours. After cooling down to room temperature, the reaction product thus obtained was dissolved in ethyl acetate, and washed with water and saturated sodium chloride aqueous solution in that order. After drying the resulting organic layer to distill off the solvent, the thus obtained residue was purified by subjecting it to silica gel column chromatography using a n-hexane/ethyl acetate mixture as an elution solvent, thereby obtaining 3.90 g of ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(6-cyano-1,2,3,4-tetrahydro-2-naphthyl)acrylate in a yellow oily form as a mixture of E and Z forms. 2.58 g of the thus obtained E/Z mixture was dissolved in 40 ml of ethanol, and the resulting solution was mixed with 650 mg of palladium oxide.1H2O.barium sulfate, and then subjected to catalytic hydrogenation under normal pressure for 5 hours. After removing the catalyst by filtration and distilling off the solvent, the resulting residue was purified by subjecting it to silica gel column chromatography using a n-hexane/ethyl acetate mixture as an elution solvent. In this way, 1.69 g of the title compound was obtained in a yellow oily form.

후처리

  1. temperatureThe thus prepared mixture was refluxed
  2. temperatureunder heating for 20 minutes
  3. customThe resulting reaction mixture
  4. temperaturerefluxed
  5. temperatureunder heating for 2 hours
  6. temperatureAfter cooling down to room temperature
  7. customthe reaction product thus obtained
  8. washwashed with water and saturated sodium chloride aqueous solution in that order
  9. customAfter drying the resulting organic layer
  10. distillationto distill off the solvent
  11. customthe thus obtained residue was purified

출처 및 근거

ORD 기록
ord-9a41d8a579e0468db56feca6d793af9d
출처 데이터셋
uspto-grants-1999_10
특허 번호
US05962695

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