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

HRID 272926Notes

Reaction equation

HRID 272926 reaction equation
[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

Participants

6

Reactant 3

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

Product 2

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-507a6e31440345c9928b74e38b2b77f1
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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