Sodium hydride → tert-butyl 4-{2-[2-(1H-imidazo[4,5-c]quinolin-1-yl)butoxy]ethyl}piperidine-1-carboxylate

HRID 430987

반응식

HRID 430987 반응식
[N:1]1([CH:14]([CH2:17][CH3:18])[CH2:15][OH:16])[C:13]2[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[N:6]=[CH:5][C:4]=2[N:3]=[CH:2]1.[H-].[Na+].I[CH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.[Cl-].[NH4+]>CN(C)C=O>[N:1]1([CH:14]([CH2:17][CH3:18])[CH2:15][O:16][CH2:22][CH2:23][CH:24]2[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])[CH2:28][CH2:29]2)[C:13]2[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[N:6]=[CH:5][C:4]=2[N:3]=[CH:2]1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 9974426Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylateHCID 218980232-(1H-imidazo[4,5-c]quinolin-1-yl)-1-butanol

생성물 1

HCID 21898028tert-butyl 4-{2-[2-(1H-imidazo[4,5-c]quinolin-1-yl)butoxy]ethyl}piperidine-1-carboxylate수율 18.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

Under a nitrogen atmosphere, 2-(1H-imidazo[4,5-c]quinolin-1-yl)butan-1-ol (6.5 g, 26.9 mmol) was added in three portions to a suspension of sodium hydride (1.4 g of 60%, 35.0 mmol) in anhydrous N,N-dimethylformamide. The reaction mixture was allowed to stir for 45 minutes by which time gas evolution had ceased. Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate (10.05 g, 29.6 mmol) was added dropwise over a period of 15 minutes. The reaction mixture was allowed to stir at ambient temperature for 2.5 hrs; then it was heated to 100° C. and stirred overnight. Analysis by HPLC showed that the reaction was about 35% complete. Saturated ammonium chloride solution was added, the resulting mixture was allowed to stir for 20 minutes and then it was extracted with ethyl acetate (2×). The ethyl acetate extracts were washed with water (2×) and then with brine, combined, dried over sodium sulfate, filtered and then concentrated under reduced pressure to provide a brown oil. The oil was purified by column chromatography (silica gel eluting sequentially with 30% ethyl acetate in hexanes, 50% ethyl acetate in hexanes, and ethyl acetate) to provide 2.2 g of tert-butyl 4-{2-[2-(1H-imidazo[4,5-c]quinolin-1-yl)butoxy]ethyl}piperidine-1-carboxylate.

후처리

  1. stirringto stir at ambient temperature for 2.5 hrs
  2. stirringstirred overnight
  3. stirringto stir for 20 minutes
  4. extractionit was extracted with ethyl acetate (2×)
  5. washThe ethyl acetate extracts were washed with water (2×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a brown oil
  10. customThe oil was purified by column chromatography (silica gel eluting sequentially with 30% ethyl acetate in hexanes, 50% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-c3780a15a19544cf90495099328dafb5
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06656938B2

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