Iodine → Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylate

HRID 1931891Notes

Reaction equation

HRID 1931891 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([Cl:12])[CH:6]=1.[C:13]([N:20]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C(=O)([O-])[O-].[Na+].[Na+]>BrC(Br)C.O1CCCC1>[Cl:12][C:7]1[CH:6]=[C:5]([C:22]2([OH:25])[CH2:23][CH2:24][N:20]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:21]2)[CH:10]=[C:9]([F:11])[CH:8]=1

Participants

8

Reactant 5

HCID 807IodineHCID 10340Sodium CarbonateHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 27362231-Bromo-3-chloro-5-fluorobenzeneHCID 5462224Magnesium

Product 1

HCID 67402932Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylateYield 35.2%

Reagents, catalysts & solvents 2

HCID 112011,1-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a slurry of magnesium turnings (0.38 g, 14.4 mmol), a small crystal of iodine and a few drops of dibromoethane in dry tetrahydrofuran (30 mL) under nitrogen was added a solution of 1-bromo-3-chloro-5-fluorobenzene (3 g, 14.4 mmol) in dry tetrahydrofuran (30 mL). The mixture was refluxed for 30 min and then cooled to ambient temperature after which a solution of 1-N-boc-3-pyrrolidone (2.9 g, 15.8 mmol) in a small amount of dry tetrahydrofuran was added. The resulting mixture was stirred at ambient temperature for 2 h after which Aqueous sodium carbonate (10%) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash column chromatography on silica gel (isooctane/ethyl acetate, 1:0 to 1:1) gave the title compound (1.6 g). MS m/z (relative intensity, 70 eV) 315 (M+, 1), 259 (99), 214 (99), 143 (65), 57 (bp).

Workup

  1. temperatureThe mixture was refluxed for 30 min
  2. additionwas added
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  5. dry with materialThe combined organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by flash column chromatography on silica gel (isooctane/ethyl acetate, 1:0 to 1:1)

Sources & evidence

ORD record
ord-a30d03a2b7f44415954bc0bdeaa02863
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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