Water → 3-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidine

HRID 1508314Notes

Reaction equation

HRID 1508314 reaction equation
C([N:8]1[CH2:12][CH2:11][C:10]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=2)([C:13]([F:16])([F:15])[F:14])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.O>ClCCCl.CO>[Cl:23][C:21]1[CH:22]=[C:17]([C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:11][CH2:12][NH:8][CH2:9]2)[CH:18]=[C:19]([Cl:24])[CH:20]=1

Participants

6

Reactant 3

HCID 962WaterHCID 5213051-Chloroethyl chloroformateHCID 582188831-Benzyl-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine

Product 1

HCID 582188803-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidineYield 89.32%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

To a stirred solution of 1-benzyl-3-(3,5-dichloro-phenyl)-3-trifluoromethyl-pyrrolidine (Preparation 34, 7.5 g, 20.1 mmol) in 1.2-dichloroethane (50 mL) was added 1-chloroethyl chloroformate (3.87 mL, 36.19 mmol) at room temperature. Resulting reaction mixture was refluxed for 3 hours. After complete consumption of starting material, reaction mixture was concentrated under reduced pressure to afford brown thick oil, which was dissolved in MeOH (50 mL) and refluxed for 2 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to afford brown oil, to which water was added (100 mL) and extracted with hexane (2×50 mL). Aqueous layer was basified by saturated sodium bicarbonate solution and extracted by ethyl acetate (3×50 mL). Combined organic layer was dried over anhydrous sodium sulfate, concentrated in vacuo to afford brown oil (7.5 g, crude). Crude compound was purified by column chromatography (100-200 mesh silica). Desired product was eluted in 25% ethyl acetate in hexane to afford product as brown oil (5.1 g, 89.32%). 1H-NMR (400 MHz, DMSO-d6) δ: 2.33-2.39 (m, 1H), 2.40-2.45 (m, 1H), 2.85-2.98 (m, 2H), 3.34 (d, 1H, J=12.72 Hz), 3.52 (d, 1H, J=12.56 Hz), 7.28-7.34 (m, 1H), 7.46-7.52 (m, 2H), 7.64 (d, 1H J=1.25 Hz). (m/z): 284.0 (M+H).

Workup

  1. customResulting
  2. customreaction mixture
  3. temperaturewas refluxed for 3 hours
  4. customAfter complete consumption of starting material, reaction mixture
  5. concentrationwas concentrated under reduced pressure
  6. customto afford brown thick oil, which
  7. temperaturerefluxed for 2 hours
  8. customAfter complete consumption of starting material, reaction mixture
  9. concentrationwas concentrated in vacuo
  10. customto afford brown oil
  11. extractionextracted with hexane (2×50 mL)
  12. extractionextracted by ethyl acetate (3×50 mL)
  13. dry with materialCombined organic layer was dried over anhydrous sodium sulfate
  14. concentrationconcentrated in vacuo
  15. customto afford brown oil (7.5 g, crude)
  16. customCrude compound was purified by column chromatography (100-200 mesh silica)
  17. washDesired product was eluted in 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d7bde8cc701c496aa223b86907e53100
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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