Water → HCID 87158563, compound

HRID 1508312Notes

Reaction equation

HRID 1508312 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.O>ClCCCl.CO>[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

6

Reactant 3

HCID 962WaterHCID 5213051-Chloroethyl chloroformateHCID 87158447HCID 87158447, compound

Product 1

HCID 87158563HCID 87158563, compoundYield 129.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

To a stirred solution of 1-benzyl-3-(3,5-dichloro-4-fluoro-phenyl)-3-trifluoromethyl-pyrrolidine (Preparation 30, 6.1 g, 15.60 mmol) in 1,2-dichloroethane (50 mL) was added 1-chloroethyl chloroformate (3.01 mL, 28.08 mmol) at room temperature. Resulting reaction mixture was refluxed for 3 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to afford brown thick oil. Brown thick oil was dissolved in MeOH (50 mL) and refluxed for 2 hours. Progress of reaction was monitored by TLC. After complete consumption of starting material, reaction mixture was again concentrated to afford brown thick oil, to which water was added (100 mL) and washed with hexane (3×50 mL). Aqueous layer was basified by saturated sodium bicarbonate solution, extracted with ethyl acetate (3×50 mL). Combined organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford product as brown thick oil (6.1 g, crude). Crude was purified by column chromatography on (100-200 mesh silica). Desired product was eluted in 25% ethyl acetate in hexane to afford brown semi solid (3.8 g, 80.68%). 1H-NMR (400 MHz, DMSO-d6) δ: 2.39-2.46 (m, 1H), 2.53-2.58 (m, 1H), 2.99-3.13 (m, 2H), 3.53 (d, 1H, J=12.84 Hz), 3.65 (d, 1H, J=12.84 Hz), 7.77 (d, 2H J=6.28 Hz). (m/z): 302.2 (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 in vacuo
  6. customto afford brown thick oil
  7. temperaturerefluxed for 2 hours
  8. customProgress of reaction
  9. customAfter complete consumption of starting material, reaction mixture
  10. concentrationwas again concentrated
  11. customto afford brown thick oil
  12. washwashed with hexane (3×50 mL)
  13. extractionextracted with ethyl acetate (3×50 mL)
  14. dry with materialCombined organic layer was dried over anhydrous sodium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-aedf1260d5784e299682280dab24561e
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

Loading…