Diisopropylamine → (1,1-dimethylethyl) 4-[[1-(phenylmethyl)-1H-benzimidazol-2-yl]carbonyl]-1-piperidinecarboxylate

HRID 1068659

반응식

HRID 1068659 반응식
CC(NC(C)C)C.C([Li])CCC.[C:13]1([CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[CH:21]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:29][C:30]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([C:42](OCC)=[O:43])[CH2:38][CH2:37]1)=[O:35])([CH3:32])[CH3:31]>C1COCC1.CCCCCC.O>[C:13]1([CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[C:21]2[C:42]([CH:39]2[CH2:40][CH2:41][N:36]([C:34]([O:33][C:30]([CH3:32])([CH3:31])[CH3:29])=[O:35])[CH2:37][CH2:38]2)=[O:43])[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

참가 물질

8

반응물 4

HCID 7912DiisopropylamineHCID 5633471-Benzyl-1H-benzimidazoleHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 178418339Butyllithium

생성물 1

HCID 54404193(1,1-dimethylethyl) 4-[[1-(phenylmethyl)-1H-benzimidazol-2-yl]carbonyl]-1-piperidinecarboxylate수율 85.8%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8058Hexane용매

반응 조건

온도
-70 °C

실험 절차

A mixture of N-(1-methylethyl)-2-propanamine (16.7 g) in THF (600ml) was stirred at −70° C. under N2 flow. Butyllithium in hexane (63 ml; 2.5 M) was added portionwise and the temperature was allowed to rise to −40° C. and stirring was continued for 15 minutes. The mixture was cooled to −70° C. and a suspension of 1-(phenylmethyl)benzimidazole (31.3 g) in THF was added dropwise. After stirring for 1 hour at −70° C., 4-(ethoxy-carbonyl)-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (42.5 g) was added dropwise and stirring at −70° C. was continued for 1.5 hours. The temperature was allowed to rise to RT and the mixture was decomposed with water, and further extracted with CH2Cl2. The organic layer was separated, dried, filtered and the solvent evaporated. The residue was crystallized from acetonitrile, yielding 54 g (85.8%) of (1,1-dimethylethyl) 4-[[1-(phenylmethyl)-1H-benzimidazol-2-yl]carbonyl]-1-piperidinecarboxylate (interm. 1; mp. 121.5° C.).

후처리

  1. customto rise to −40° C.
  2. stirringstirring
  3. temperatureThe mixture was cooled to −70° C.
  4. additionwas added dropwise
  5. stirringAfter stirring for 1 hour at −70° C.
  6. stirringstirring at −70° C.
  7. waitwas continued for 1.5 hours
  8. customto rise to RT
  9. extractionfurther extracted with CH2Cl2
  10. customThe organic layer was separated
  11. customdried
  12. filtrationfiltered
  13. customthe solvent evaporated
  14. customThe residue was crystallized from acetonitrile

출처 및 근거

ORD 기록
ord-6a597f9831c94771a51b2b9fbad82102
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06251894B1

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