Methanol → 3-(2,3-Difluorophenyl)-3-fluoropyrrolidine

HRID 1931813Notes

Reaction equation

HRID 1931813 reaction equation
C([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=2[F:21])([F:13])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)=O)C.CO>ClCCCl>[F:21][C:15]1[C:16]([F:20])=[CH:17][CH:18]=[CH:19][C:14]=1[C:10]1([F:13])[CH2:11][CH2:12][NH:8][CH2:9]1

Participants

5

Reactant 3

HCID 887MethanolHCID 5213051-Chloroethyl chloroformateHCID 685171501-Benzyl-3-(2,3-difluorophenyl)-3-fluoropyrrolidine

Product 1

HCID 251438113-(2,3-Difluorophenyl)-3-fluoropyrrolidineYield 19.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1-benzyl-3-(2,3-difluorophenyl)-3-fluoropyrrolidine (1.6 g, 5.5 mmol) in dry 1,2-dichloroethane (10 mL) under nitrogen was added 1-chloroethylchloroformate (600 μl, 5.5 mmol). The mixture was stirred at ambient temperature for 7 h after which methanol was added and the mixture was evaporated. Methanol (10 mL) was added and the mixture was heated at reflux for 4 h. The mixture was evaporated and purified by column chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1) to give the title compound (214 mg). The amine was converted to the hydrochloric acid salt and recrystallized from ethanol/diethyl ether: M.p. 136° C.; MS m/z (relative intensity, 70 eV) 201 (M+, 35), 151 (bp), 158 (69), 138 (45), 133 (42).

Workup

  1. additionwas added
  2. customthe mixture was evaporated
  3. additionMethanol (10 mL) was added
  4. temperaturethe mixture was heated
  5. temperatureat reflux for 4 h
  6. customThe mixture was evaporated
  7. custompurified by column chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1)

Sources & evidence

ORD record
ord-5c37fa550b25455f978fc3d3ea5c2e6a
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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