Methanol → HCID 87158563, compound

HRID 2206929Notes

Reaction equation

HRID 2206929 reaction equation
C([N:8]1[CH2:12][CH2:11][C:10]([C:17]2[CH:22]=[C:21]([Cl:23])[C:20]([F:24])=[C:19]([Cl:25])[CH:18]=2)([C:13]([F:16])([F:15])[F:14])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.CO.COC(C)(C)C>ClCCCl.O>[Cl:25][C:19]1[CH:18]=[C:17]([C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:11][CH2:12][NH:8][CH2:9]2)[CH:22]=[C:21]([Cl:23])[C:20]=1[F:24]

Participants

7

Reactant 4

HCID 887MethanolHCID 15413tert-Butyl methyl etherHCID 5213051-Chloroethyl chloroformateHCID 87158447HCID 87158447, compound

Product 1

HCID 87158563HCID 87158563, compoundYield 91.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

1-Benzyl-3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)pyrrolidine (3.7 g) was dissolved in 1,2-dichloroethane (20 ml), added with 1-chloroethyl chloroformate (2.7 g) at room temperature, and then refluxed under heating for 3 hours. The reaction solution was concentrated under reduced pressure, and the residue obtained was added with methanol (30 ml) and further refluxed under heating for 2 hours. The reaction solution was concentrated under reduced pressure and the residue obtained was added with t-butyl methyl ether and water to separate the aqueous layer. After that, the organic layer was again washed with a 1 M aqueous solution of hydrochloric acid, and the aqueous layers were combined, added with a saturated aqueous solution of potassium carbonate to make the liquid alkaline, and extracted with t-butyl methyl ether. The aqueous phase was extracted again with t-butyl methyl ether, and the organic layers were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain 3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)pyrrolidine (2.6 g).

Workup

  1. temperaturerefluxed
  2. temperatureunder heating for 3 hours
  3. concentrationThe reaction solution was concentrated under reduced pressure
  4. customthe residue obtained
  5. temperaturefurther refluxed
  6. temperatureunder heating for 2 hours
  7. concentrationThe reaction solution was concentrated under reduced pressure
  8. customthe residue obtained
  9. customto separate the aqueous layer
  10. washAfter that, the organic layer was again washed with a 1 M aqueous solution of hydrochloric acid
  11. additionadded with a saturated aqueous solution of potassium carbonate
  12. extractionextracted with t-butyl methyl ether
  13. extractionThe aqueous phase was extracted again with t-butyl methyl ether
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9482fe2dac3641f791efa3b24f3ce8cf
Source dataset
uspto-grants-2016_06
Patent number
US09375000B2

Reaction notes

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