Potassium Iodide → HCID 2057368, compound

HRID 852071Notes

Reaction equation

HRID 852071 reaction equation
[O:1]([CH2:8][CH2:9][CH2:10]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[K+].[NH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C([O-])=O.[NH4+]>C(#N)C.O>[O:1]([CH2:8][CH2:9][CH2:10][N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 8082PiperidineHCID 68522Benzene, (3-bromopropoxy)-2×HCID 2723923Ammonium formate

Product 1

HCID 2057368HCID 2057368, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

Mix 3-phenoxypropyl bromide (801.5 g, 3.73 mol), potassium iodide (61.8 g, 0.37 mol, 0.10 equivalents) and water (4.0 L) in a 12-L, 3-necked flask fitted with: a stirrer, thermometer in a side-arm adapter, connected to a Firestone® valve and an addition funnel fitted with a gas outlet adapter, connected to a bubbler. Add piperidine (634.6 g, 7.45 mol, 2.0 equivalents) over 1 hour, without cooling under nitrogen. The temperature at the end of the addition is 40° C. Heat the reaction mixture and maintain the temperature at 50° C. for 6 hours. Monitor the progress of the reaction by HPLC (Column=300×3.9 mm Phenomenex Bondclone 10 CN; mobile phase=65% acetonitrile:35% 0.1N ammonium formate buffer; flow=1.5 mL/minute; wavelength=215 nm; RT: 3-phenoxypropyl bromide=2.3 minutes; 37=4.4 minutes). Typically, the conversion is 94%. Cool the reaction mixture to ambient temperature over a time period of 14 hours and extract with dichloromethane (2×4.0 L). Combine the organic extracts and dry over MgSO4 (400 g). Filter off the drying agent and wash with dichloromethane (1.0 L). Concentrate the filtrate (35-40° C./50 torr) to give 800 g, 98% Yield) of 4, as an oil. HPLC analysis shows that 37 is 90% pure. Purify 4 (16.5 g portion) by distillation under vacuum and collect the title compound (10 g) as a colorless liquid at 99-105° C./0.3 mm: 1H NMR (CDCl3, 200 MHz) δ 1.38-1.5 (m, 2H), 1.5-1.64 (m, 4H), 1.9-2.1 (m, 6H), 4.0 (t, 2H), 6.85-6.95 (m. 3H), 7.22-7.3 (t, 2H). Analysis calculated for C14H21NO: C, 76.67; H, 9.65; 6.39. Found: C, 76.55; H, 9.50; N, 6.22. [M+H]+=220 m/e.

Workup

  1. customfitted with: a stirrer
  2. customthermometer in a side-arm adapter, connected to a Firestone® valve and an addition funnel
  3. customfitted with a gas outlet adapter
  4. temperaturewithout cooling under nitrogen
  5. additionThe temperature at the end of the addition
  6. customis 40° C
  7. temperatureHeat the reaction mixture
  8. temperatureCool the reaction mixture to ambient temperature over a time period of 14 hours
  9. extractionextract with dichloromethane (2×4.0 L)
  10. dry with materialCombine the organic extracts and dry over MgSO4 (400 g)
  11. filtrationFilter off the drying agent
  12. washwash with dichloromethane (1.0 L)
  13. concentrationConcentrate the filtrate (35-40° C./50 torr)
  14. customto give 800 g, 98% Yield) of 4
  15. customPurify 4 (16.5 g portion)
  16. distillationby distillation under vacuum
  17. customcollect the title compound (10 g) as a colorless liquid at 99-105° C./0.3 mm

Sources & evidence

ORD record
ord-8ff8be83e22a46438a10591c5c41c889
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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