Hydrochloric Acid → 1-(3-Bromo-5-ethoxy-phenyl)-pyrrolidine

HRID 1677528Notes

Reaction equation

HRID 1677528 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:5]=[C:6]([O:8][CH2:9]OC)[CH:7]=1.Cl.[OH-].[NH4+].[C:20]([O-])([O-])=O.[K+].[K+].C(I)C>C(Cl)Cl.CO.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:5]=[C:6]([O:8][CH2:9][CH3:20])[CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6340Iodoethane3×HCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 595410311-(3-Bromo-5-methoxymethoxy-phenyl)-pyrrolidine

Product 1

HCID 595408171-(3-Bromo-5-ethoxy-phenyl)-pyrrolidineYield 44.2%

Reagents, catalysts & solvents 3

HCID 887MethanolCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

A flask was charged with 1-(3-bromo-5-methoxymethoxy-phenyl)-pyrrolidine (206 mg, 0.72 mmol) and a solution of 10% ethanolic hydrogen chloride (5 ml, dry) was added. The flask was capped and stirred for 45 minutes. The volatile material was stripped (rotovap) and methylene chloride (10 ml) was added. This was again stripped. The remainder was taken up in methylene chloride (10 ml). To this stirred material was added a 5% solution of ammonium hydroxide in methanol (20 drops). This material was stripped and the procedure repeated once more. The stripped remainder was taken up in dry DMF (3 ml) and K2CO3 (348 mg, 2.52 mmol) was added. Ethyl iodide (0.07 ml, 0.9 mmol) was added and the mixture was capped and stirred for 2.5 hours. Additional ethyl iodide (0.15 ml, 1.9 mmol) was added and the material was capped and heated (60° C.) over night. Ethyl iodide (0.15 ml, 1.9 mmol) was again added and the mixture capped and heated (100° C.) for 12 hours. The volatiles were removed (rotovap/pump) and the remainder was taken up in water (25 ml) and ethyl acetate (25 ml) and the material shaken in a separtatory funnel. The organic phase was collected and the aqueous phase was back extracted with ethyl acetate (2×20 ml), the organics combined, dried (MgSO4), filtered and stripped to provide a crude oil. The oil was purified by preparative TLC using 7% EtOAc in hexanes as eluant to provide 86 mg of 1-(3-bromo-5-ethoxy-phenyl)-pyrrolidine as a golden brown semi-viscous oil.

Workup

  1. customThe flask was capped
  2. additionwas added
  3. customthe mixture was capped
  4. stirringstirred for 2.5 hours
  5. customthe material was capped
  6. customthe mixture capped
  7. temperatureheated (100° C.) for 12 hours
  8. customThe volatiles were removed (rotovap/pump)
  9. stirringethyl acetate (25 ml) and the material shaken in a separtatory funnel
  10. customThe organic phase was collected
  11. extractionthe aqueous phase was back extracted with ethyl acetate (2×20 ml)
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. customto provide a crude oil
  15. customThe oil was purified by preparative TLC

Sources & evidence

ORD record
ord-35520da9d5d24f6a8618ae724501213b
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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