4-Toluenesulfonyl chloride → tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1630007노트

반응식

HRID 1630007 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=O)[CH:10](C([O-])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Na+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.Cl[C:32](=[CH2:35])[C:33]#[N:34].C(N(CC)CC)C>ClCCl.O>[C:33]([C:32]1[CH:35]=[CH:14][N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C:10]=12)#[N:34]

참가 물질

7

반응물 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 701982-ChloroacrylonitrileHCID 59437097Sodium 4-(tert-butoxycarbonyl)-1-formylpiperazine-2-carboxylate

생성물 1

HCID 86680813tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate수율 69.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

To a solution under nitrogen of 28.7 g (102 mmol) of sodium 4-(tert-butyloxycarbonyl)-1-formylpiperazine-2-carboxylate (CAS 1108698-36-7) in 1 l of dichloromethane are added 21.5 g (113 mmol) of p-toluenesulfonyl chloride. After stirring for 40 minutes, 8.2 ml (102 mmol) of 2-chloroacrylonitrile are added. After stirring for 40 minutes, 32.8 ml (235 mmol) of triethylamine are added dropwise and the mixture is stirred overnight at room temperature, and then refluxed for 1 hour. The solution is then cooled to room temperature. 150 ml of water are added. The organic phase is separated out by settling, washed twice with 100 ml of water, dried over sodium sulfate and filtered, and concentrated under reduced pressure. The residue obtained is chromatographed on a column of silica gel, eluting with a mixture of 0 to 10% ethyl acetate in dichloromethane, to give 17.5 g of tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after dissolving in a mixture of cyclohexane and dichloromethane and then precipitating by slow concentration and drying under reduced pressure.

후처리

  1. stirringAfter stirring for 40 minutes
  2. stirringthe mixture is stirred overnight at room temperature
  3. temperaturerefluxed for 1 hour
  4. customThe organic phase is separated out
  5. washwashed twice with 100 ml of water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue obtained
  10. customis chromatographed on a column of silica gel
  11. washeluting with a mixture of 0 to 10% ethyl acetate in dichloromethane

출처 및 근거

ORD 기록
ord-c0f45c90f19f489c8b9a9ce283cb8c9c
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791119B2

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