Hydrochloric Acid → 1-(4,5-Dihydro-1,3-thiazol-2-yl)azetidine-3-thiol

770 mg of 28% sodium methoxide-methanol solution was added to a mixture solution of 862 mg of Compound (18) obtained in the step (b) in 20 ml of anhydrous methanol under ice-cooling and nitrogen gas atmosphere. Then the reaction mixture was stirred for 10 minutes under the same conditions. After reaction, 4 ml of 2N--HCl was added to the reaction mixture and the solvent was removed under reduced pressure to give crude 3-mercapto-1-(thiazolin-2-yl)azetidine [Compound (19)]. Then the crude Compound (19) was dissolved in 15 ml of a mixture solution of anhydrous acetonitrile-chloroform and to this solution were added 2430 mg of p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate [Compound (20)] and 2.8 ml of diisopropylethylamine under ice-cooling and nitrogen gas atmosphere. After stirring the reaction mixture for 2 hours under the same conditions, ethyl acetate was added and the separated organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated saline solution. The solvent was removed and the resulting residue was purified by silica gel column chromatography (chloroform: acetone =1:2) to give 1339 mg [65% yield from Compound (18)] of p-nitrobenzyl (1R,5S,6S)-2-[(1-(thiazolin-2-yl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate [Compound (21)].

1. temperaturecooling
2. customAfter reaction, 4 ml of 2N
3. customthe solvent was removed under reduced pressure

ORD record

ord-02a28832ca344256b2eba80a6a2a97ce

Source dataset

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05886172