Potassium bis(trimethylsilyl)amide → Tert-butyl 3-(4-bromo-2-methylphenyl)pyrrolidine-1-carboxylate

HRID 503911Notes

Reaction equation

HRID 503911 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Br:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:19][CH2:20]OS(C)(=O)=O)=[C:14]([CH3:35])[CH:13]=1>C1COCC1>[C:31]([O:30][C:28]([N:27]1[CH2:20][CH2:19][CH:18]([C:15]2[CH:16]=[CH:17][C:12]([Br:11])=[CH:13][C:14]=2[CH3:35])[CH2:26]1)=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 86621498Methanesulfonic acid 3-(4-bromo-2-methyl-phenyl)-4-tert-butoxycarbonylamino-butyl ester

Product 1

HCID 66877329Tert-butyl 3-(4-bromo-2-methylphenyl)pyrrolidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

KHMDS (0.5 M in toluene, 186 mL, 0.09303 mol) was added at 0° C. to methanesulfonic acid 3-(4-bromo-2-methyl-phenyl)-4-tert-butoxycarbonylamino-butyl ester (36.9 g, 0.08457 mol) dissolved in THF (400 mL). The ice-bath was removed and the mixture was stirred at room temperature for 2 hours. A saturated solution of NH4Cl was added to the reaction mixture and the resulting mixture was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified via flash chromatography (hexane/EtOAc, 8/2) to give 27.3 g (95% yield) of 3-(4-bromo-2-methyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a clear oil.

Workup

  1. customThe ice-bath was removed
  2. additionA saturated solution of NH4Cl was added to the reaction mixture
  3. extractionthe resulting mixture was extracted with EtOAc
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified via flash chromatography (hexane/EtOAc, 8/2)

Sources & evidence

ORD record
ord-115c77264bbc423fabf542c78282a3ce
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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