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

HRID 2376115ノート

反応式

HRID 2376115 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-64646d4e269d47b2aaf217658d588247
出典データセット
uspto-grants-2008_12
特許番号
US07465731B2

反応ノート

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