(4R)-1-t-butoxycarbonyl-4-(p-toluenesulfonyloxy)-N-t-butyl-L-prolinamide → (1S,4S)-5-t-Butoxycarbonyl-2-t-butyl-2,5-diazabicyclo[2.2.1]heptan-3-one

HRID 1780276Notes

Reaction equation

HRID 1780276 reaction equation
C([Mg]Br)C1C=CC=CC=1.[C:10]([O:14][C:15]([N:17]1[CH2:28][C@H:27](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:26][C@H:18]1[C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:16])([CH3:13])([CH3:12])[CH3:11]>O1CCCC1>[C:10]([O:14][C:15]([N:17]1[CH2:28][C@@H:27]2[CH2:26][C@H:18]1[C:19](=[O:20])[N:21]2[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

4

Reactant 2

HCID 86750836(4R)-1-t-butoxycarbonyl-4-(p-toluenesulfonyloxy)-N-t-butyl-L-prolinamideHCID 178419663HCID 178419663, compound

Product 1

HCID 57047123(1S,4S)-5-t-Butoxycarbonyl-2-t-butyl-2,5-diazabicyclo[2.2.1]heptan-3-oneYield 42.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2.28 ml (4.56 mmol) of a 2M solution of benzylmagnesium bromide in tetrahydrofuran were added dropwise, whilst ice-cooling, to a solution of 1 g (2.27 mmol) of (4R)-1-t-butoxycarbonyl-4-(p-toluenesulfonyloxy)-N-t-butyl-L-prolinamide [prepared as described in Preparation 6(a)] in 15 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 3 hours. At the end of this time, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic extract was washed with a 10% w/v aqueous solution of citric acid, with a 10% w/v aqueous of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. The mixture was dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using a 1:3 by volume mixture of ethyl acetate and hexane as the eluent. The resulting crude product was recrystallized from a mixture of methylene chloride, diethyl ether and hexane, to give 260 mg of the title compound as colorless crystals, melting at 167°-168° C.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with a 10% w/v aqueous solution of citric acid, with a 10% w/v aqueous of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. customafter which the solvent was removed by distillation under reduced pressure
  6. customThe residue was purified by column chromatography through silica gel
  7. additionby volume mixture of ethyl acetate and hexane as the eluent
  8. customThe resulting crude product was recrystallized from a mixture of methylene chloride, diethyl ether and hexane

Sources & evidence

ORD record
ord-2323e2dbd66c4488b7cd58d7d439d296
Source dataset
uspto-grants-1997_05
Patent number
US05629406

Reaction notes

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