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 489789ノート

反応式

HRID 489789 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a5e925da187f48d5a661b8d266beba12
出典データセット
uspto-grants-2005_12
特許番号
US06979690B2

反応ノート

読み込み中…