2,6-Dibromopyridine → 2-Bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine

HRID 30215

반응식

HRID 30215 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.C([Li])CCC.[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([C:27](N(OC)C)=[O:28])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[OH-].[Na+]>ClCCl.CCCCCC>[Br:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:27]([CH:24]2[CH2:25][CH2:26][N:21]([C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[CH2:22][CH2:23]2)=[O:28])[N:3]=1

참가 물질

7

반응물 4

HCID 122742,6-DibromopyridineHCID 14798Sodium HydroxideHCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 866009232-Bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine수율 100.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매3회HCID 8058Hexane용매

반응 조건

온도
-78 °C

실험 절차

Dissolve 2,6-dibromopyridine (3.6 g, 15.3 mmol) in anhydrous dichloromethane (90 mL) under nitrogen atmosphere. Cool the reaction mixture to −78° C. Add a solution of n-butyl lithium in hexane very slowly via a syringe (1.6 M, 10.5 mL, 16.9 mmol). After the addition is complete, stir the reaction at −78° C. for 1 hr. Add a solution of 4-(methoxy-methyl-aminocarbonyl)-piperidine-1-carboxylic acid tert-butyl ester (2 g, 7.3 mmol) in anhydrous dichloromethane (10 mL) dropwise to the reaction mixture. Stir the reaction at −78° C. for 2 hrs., then allow it to slowly warm to room temperature overnight. Quench the reaction with 0.1 N aqueous NaOH. Dilute the solution with dichloromethane (100 mL), transfer into a separation funnel and shake with 0.1 N NaOH (60 mL). Separate the organic layer and dry it over anhydrous sodium sulfate. Evaporate the solvent under reduced pressure. Further purify the residue by chromatography on silica gel column (10%-30% ethyl acetate/hexane) to obtain 2-bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine (2.7 g, quantitative yield). Mass spectrum (ion spray): m/z 370 (M+1).

후처리

  1. additionAfter the addition
  2. customthe reaction at −78° C. for 1 hr
  3. stirringStir
  4. customthe reaction at −78° C. for 2 hrs
  5. temperatureto slowly warm to room temperature overnight
  6. customQuench
  7. customthe reaction with 0.1 N aqueous NaOH
  8. customSeparate the organic layer
  9. dry with materialdry it over anhydrous sodium sulfate
  10. customEvaporate the solvent under reduced pressure
  11. customFurther purify the residue by chromatography on silica gel column (10%-30% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-4a42d37400dd41e4aa31b216411a6e87
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423050B2

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