Sodium hydride → (2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acid

HRID 458387Notes

Reaction equation

HRID 458387 reaction equation
[CH2:1]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].[C:23]([O:27][C:28]([N:30]1[CH2:34][C:33](=O)[CH2:32][C@H:31]1[C:36]([OH:38])=[O:37])=[O:29])([CH3:26])([CH3:25])[CH3:24].C([O-])(O)=O.[Na+]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:23]([O:27][C:28]([N:30]1[CH2:34][C:33](=[CH2:1])[CH2:32][C@H:31]1[C:36]([OH:38])=[O:37])=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 137960MethylenetriphenylphosphoraneHCID 516892Sodium BicarbonateHCID 11593804(2S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid

Product 1

HCID 21727417(2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acidYield 72%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methylenetriphenyl phosphorane, previously prepared from 37 g (777 mmol, 50% NaH in mineral oil, 4 eq) and 277.6 g (777 mmol, 4 eq) methyltriphenyl-phosphonium bromide in 1.51 THF by stirring at 50° C. for 4 h, were added 44.5 g (194 mmol, 1 eq) (2S)-4-Oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester in 300 ml over a period of 30 min at RT. The suspension was stirred at 50° C. over night. After cooling to RT the suspension was added to a 5% NaHCO3 solution, washed with ether, the inorganic phase was acidified and extracted with EtOAc, washed with brine, dried over Na2SO4 and evaporated. 32.1 g (72%) (2S)-4-Methylene-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester were isolated as white solid.

Workup

  1. stirringThe suspension was stirred at 50° C. over night
  2. temperatureAfter cooling to RT the suspension
  3. washwashed with ether
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-1783aad2aab04e65b81d9ae8d2d19d94
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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