Tert-butyl 4-(3-oxopropyl)piperidine-1-carboxylate → 1,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-hydroxypropyl)-1-piperidinecarboxylate

HRID 489789노트

반응식

HRID 489789 반응식
[F:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[O:20]=[CH:21][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>O1CCCC1>[CH3:12][C:10]([CH3:11])([CH3:13])[C:9]([NH:8][C:6]1[N:7]=[C:2]([F:1])[C:3]([CH:21]([OH:20])[CH2:22][CH2:23][CH:24]2[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:28][CH2:29]2)=[CH:4][CH:5]=1)=[O:14]

참가 물질

5

반응물 3

HCID 10657745Tert-butyl 4-(3-oxopropyl)piperidine-1-carboxylateHCID 131542516-Fluoro-2-pivaloylaminopyridineHCID 178418339Butyllithium

생성물 1

HCID 222626141,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-hydroxypropyl)-1-piperidinecarboxylate수율 34%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

To a solution of N-(6-fluoro-2-pyridinyl)-2,2-dimethylpropanamide (Turner, James A., J. Org. Chem., 1983, 48, 3401–3408, 1.15 g, 5.87 mmol) in tetrahydrofuran (15 ml) was added dropwise a solution of n-butyllitium (8.1 ml, 12.9 mmol) at −78° C. over 10 min., and the mixture was stirred at 0° C. for 1 h. After cooling to −78° C., a solution of 1,1-dimethylethyl 4-(3-oxopropyl)-1-piperidinecarboxylate (Keenan, Richard M. et. al, J. Med. Chem., 1999, 42, 545–559, 1.70 g, 7.04 mmol) in tetrahydrofuran (5 ml) was added to the mixture. After stirring for 0.5 h, the mixture was allowed to warm up to room temperature and stirred for further 2 h. The mixture was quenched with water (20 ml) and extracted with ethyl acetate (100 ml). The organic layer was washed with brine (50 ml) and dried over magnesium sulfate. Removal of solvent gave brown oily residue, which was chromatographed on a column of silica gel eluting with ethyl acetate/hexane (2:1) to afford 0.86 g (34%) of the title compound as a pale yellow amorphous solid.

후처리

  1. temperatureAfter cooling to −78° C.
  2. stirringAfter stirring for 0.5 h
  3. temperatureto warm up to room temperature
  4. stirringstirred for further 2 h
  5. customThe mixture was quenched with water (20 ml)
  6. extractionextracted with ethyl acetate (100 ml)
  7. washThe organic layer was washed with brine (50 ml)
  8. dry with materialdried over magnesium sulfate
  9. customRemoval of solvent
  10. customgave brown oily residue, which
  11. customwas chromatographed on a column of silica gel eluting with ethyl acetate/hexane (2:1)

출처 및 근거

ORD 기록
ord-a5e925da187f48d5a661b8d266beba12
출처 데이터셋
uspto-grants-2005_12
특허 번호
US06979690B2

반응 노트

불러오는 중…