Ethyl Acetate → ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinate

HRID 2376115노트

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HRID 2376115 반응식
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[NH2:14][C@@H:15]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C.O>[C:23]([O:22][C:20]([N:17]1[CH2:18][CH2:19][C@@H:15]([NH:14][C:3]2[C:2]([Cl:1])=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:4]=2)[CH2:16]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

참가 물질

7

반응물 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 16762519Ethyl 5,6-Dichloronicotinate

생성물 1

HCID 68959254ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinate수율 78.5%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

A mixture of ethyl 5,6-dichloronicotinate (5.0 g), tert-butyl (3R)-3-amino-1-pyrrolidinecarboxylate (5.08 g) and K2CO3 (4.71 g) in DMF (40 ml) was stirred at 100° C. for 12 hours under atmospheric pressure of nitrogen. The reaction mixture was poured into a mixture of AcOEt and H2O and the organic layer was washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with n-Hexane-AcOEt (9:1). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinate (6.6 g).

후처리

  1. washthe organic layer was washed with brine
  2. dry with materialdried over MgSO4
  3. customThe solvent was evaporated in vacuo
  4. customthe residue was chromatographed on silicagel
  5. washeluting with n-Hexane-AcOEt (9:1)
  6. additionThe eluted fractions containing the desired product
  7. customwere collected
  8. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-64646d4e269d47b2aaf217658d588247
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07465731B2

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