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

HRID 272926노트

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HRID 272926 반응식
[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

참가 물질

6

반응물 3

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

생성물 2

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-507a6e31440345c9928b74e38b2b77f1
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456164B2

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