1,4-Dibromobutane → 1-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]cyclo-pentane-carbonitrile

HRID 272926ノート

反応式

HRID 272926 の反応式
[H-].[Na+].[N:3]1([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]#[N:20])=[CH:14][CH:13]=2)[CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:22][CH2:23][CH2:24][CH2:25]Br>CN(C=O)C>[NH3:3].[N:3]1([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3([C:19]#[N:20])[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:16][CH:17]=2)[CH2:4][CH2:5][CH2:6][CH2:7]1

参加物

6

反応物 3

HCID 80561,4-DibromobutaneHCID 24758Sodium hydrideHCID 23091635[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]acetonitrile

生成物 2

HCID 222AmmoniaHCID 230916111-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]cyclo-pentane-carbonitrile収率 72.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒3 回

反応条件

温度
0 °C

実験手順

To a suspension of NaH (60%, 0.574 g, 14.35 mmol) in DMF (8 mL) at 0° C. was added dropwise [4-(3-pyrrolidin-1-ylpropoxy)phenyl]acetonitrile (1 g, 4.10 mmol) in DMF (3 mL). The reaction mixture was stirred at 0° C. for 5 min than at room temperature for 30 min. After cooling to 0° C., 1,4-dibromobutane (0.980 mL, 8.2 mmol) in DMF (2 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature then heated to 50° C. overnight. It was poured into ice-cold water and extracted with DCM. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude mixture was purified by column chromatography, eluting with a gradient of DCM:MeOH:NH3 (from 99:0:1 to 90:10:1) to give the title compound (0.443 g, 36%). 1H NMR (400 MHz, DMSO-d6) δ7.29 (d, 2H), 6.79 (d, 2H), 4.02 (m, 2H), 3.18 (m, 2H), 2.47-2.28 (m, 4H), 2.19-1.75 (m, 11H), 1.19 (m, 3H).

後処理

  1. temperatureAfter cooling to 0° C.
  2. temperatureto warm up to room temperature
  3. temperaturethen heated to 50° C. overnight
  4. additionIt was poured into ice-cold water
  5. extractionextracted with DCM
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude mixture was purified by column chromatography
  11. washeluting with a gradient of DCM

出典と根拠

ORDレコード
ord-507a6e31440345c9928b74e38b2b77f1
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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