(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
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
Product 1
Reagents, catalysts & solvents 1
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.