Iodine → 1-Benzyl-3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol

HRID 1931887Notes

Reaction equation

HRID 1931887 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Cl:9])[CH:3]=1.[Mg].II.[CH2:13]([N:20]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:13]([N:20]1[CH2:24][CH2:23][C:22]([C:2]2[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Cl:9])[CH:3]=2)([OH:25])[CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 698901-Benzyl-3-pyrrolidinoneHCID 27362231-Bromo-3-chloro-5-fluorobenzeneHCID 5462224Magnesium

Product 1

HCID 685158581-Benzyl-3-(3-chloro-5-fluorophenyl)pyrrolidin-3-olYield 12.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-bromo-3-chloro-5-fluorobenzene (5 g, 23.9 mmol) in dry tetrahydrofuran (50 mL), under nitrogen, was added magnesium turnings (0.58 g, 26.2 mmol) and one crystal of iodine. The mixture was heated until self sustained reflux started. When the reflux ceased a solution of 1-N-benzyl-3-pyrrolidone (4.17 g, 23.9 mmol) in dry tetrahydrofuran (50 mL) was added drop wise. The resulting mixture was stirred at ambient temperature for 15 min after which aqueous saturated ammonium chloride solution (40 mL) was added. The aqueous phase was extracted with tert-butyl methyl ether the combined organic phases were extracted with aqueous HCl (10%, 200 mL), the aqueous phase was basified with aqueous NaOH (5 M) and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was dried (MgSO4), filtered and evaporated. Purification on silica gel (isooctane/ethyl acetate, 1:1 to 0:1) gave the title compound (0.92 g).

Workup

  1. temperatureThe mixture was heated until self
  2. temperaturesustained reflux
  3. additionwas added drop wise
  4. additionwas added
  5. extractionThe aqueous phase was extracted with tert-butyl methyl ether the combined organic phases
  6. extractionwere extracted with aqueous HCl (10%, 200 mL)
  7. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  8. dry with materialThe combined organic phase was dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customPurification on silica gel (isooctane/ethyl acetate, 1:1 to 0:1)

Sources & evidence

ORD record
ord-01d5371ff2414079b05d84056515d943
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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