Methyl iodide → HCID 10109651, compound

HRID 586621Notes

Reaction equation

HRID 586621 reaction equation
Cl[S:2]([OH:5])(=O)=[O:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[C:19]3[N:15]([CH2:16][CH2:17][CH2:18]3)[C:14]=2[CH3:27])=[CH:9][CH:8]=1.S(Cl)(Cl)(=O)=O.[O-]S([O-])=O.[Na+].[Na+].[C:39]([O-])(O)=O.[Na+].CI>C(Cl)(Cl)Cl.C(O)C>[F:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[C:20]([C:21]3[CH:22]=[CH:23][C:24]([S:2]([CH3:39])(=[O:5])=[O:3])=[CH:25][CH:26]=3)=[C:19]3[N:15]([C:14]=2[CH3:27])[CH2:16][CH2:17][CH2:18]3)=[CH:11][CH:12]=1

Participants

9

Reactant 6

HCID 6328Methyl iodideHCID 24437Sodium SulfiteHCID 24638Chlorosulfonic acidHCID 24648Sulfuryl chlorideHCID 516892Sodium BicarbonateHCID 22335603HCID 22335603, compound

Product 1

HCID 10109651HCID 10109651, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent2×

Conditions

Temperature
0 °C

Procedure

Chlorosulphonic acid (7 g, 60 mmol) is added dropwise to a solution of 6-(4-fluorophenyl)-5-methyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (2.91 g, 10 mmol) in CHCl3 (12 ml) cooled to 0° C. with further cooling and the mixture is heated under reflux (66° C.) for 3 h after addition is complete. The reaction mixture is then poured onto ice water (0.4 kg) and the sulphonyl chloride depositing is taken up in chloroform (150 ml). The ice-water phase is extracted with chloroform (100 ml). These CHCl3 extracts are dried using Na2SO4 sicc. and concentrated. The residue is treated with an aqueous solution (25 ml) of Na2SO3 (1.42 g, 11.2 mmol) and NaHCO3 (1.89 g, 22.5 mmol) and heated at 70° C. (IT) for 2 h. After addition of ethanol (25 ml) and methyl iodide (1.0 ml, 2.27 g, 16 mmol), the temperature is increased to 100° C. (IT) and maintained for a further 2 h (reflux). After the cooling of the mixture, deposited solid is filtered off with suction, washed with water (10 ml) and dried over P2O5 in vacuo: 0.4 g (11%) of the product having a melting point of 191° C. (97% purity) results. The aqueous-ethanolic phase is extracted with ethyl acetate (50 ml) and the filtrate is concentrated after drying with Na2SO4 sicc. The residue crystallizes from EtOH (5 ml): 0.5 g (14% of theory, 94% purity) results.

Workup

  1. temperaturewith further cooling
  2. temperaturethe mixture is heated
  3. temperatureunder reflux (66° C.) for 3 h
  4. additionafter addition
  5. additionThe reaction mixture is then poured onto ice water (0.4 kg)
  6. extractionThe ice-water phase is extracted with chloroform (100 ml)
  7. dry with materialThese CHCl3 extracts are dried
  8. concentrationand concentrated
  9. temperatureheated at 70° C. (IT) for 2 h
  10. temperaturethe temperature is increased to 100° C. (IT)
  11. temperaturemaintained for a further 2 h
  12. temperature(reflux)
  13. temperatureAfter the cooling of the mixture
  14. filtrationis filtered off with suction
  15. washwashed with water (10 ml)
  16. dry with materialdried over P2O5 in vacuo
  17. customresults
  18. extractionThe aqueous-ethanolic phase is extracted with ethyl acetate (50 ml)
  19. concentrationthe filtrate is concentrated
  20. dry with materialafter drying with Na2SO4 sicc
  21. customThe residue crystallizes from EtOH (5 ml)
  22. custom0.5 g (14% of theory, 94% purity) results

Sources & evidence

ORD record
ord-2453e8391a174a4ca43b1e66b67a0821
Source dataset
uspto-grants-2005_08
Patent number
US06936632B2

Reaction notes

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