135693-13-9

Upstream product

• 123-75-1 pyrrolidine 
• 135693-14-0 3-[(2R,3S)-1-Carboxymethyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-azetidin-2-yl]-propionic acid ethyl ester 
• 135382-83-1 (2S,3R)-3-[(2S,3S)-1-tert-Butoxycarbonylmethyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-azetidin-2-yl]-oxirane-2-carboxylic acid ethyl ester 
• 140925-22-0 (E)-3-[(2R,3S)-1-tert-Butoxycarbonylmethyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-azetidin-2-yl]-acrylic acid ethyl ester 
• 140866-85-9 (2S,3R)-3-[(E)-tert-Butoxycarbonylmethylimino-methyl]-oxirane-2-carboxylic acid ethyl ester 
• 140925-20-8 (2S,3S)-3-formyloxirane-2-carboxylic acid ethyl ester 
• 136171-94-3 (2S,3R)-2,3-epoxy-4-hydroxybutanoic acid ethyl ester 
• 139165-11-0 3-[(2R,3S)-1-tert-Butoxycarbonylmethyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-azetidin-2-yl]-propionic acid ethyl ester 

Downstream Products

• 139165-12-1 (6R,7S)-3-Chloro-7-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-8-oxo-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 4-nitro-benzyl ester 
• 76497-76-2 (6R*,7S*)-3-chloro-7-amino-8-oxo-1-azabicyclo<4.2.0>oct-2-en-2-carboxylic acid 
• 140866-86-0 3-{(2R,3S)-1-Carboxymethyl-4-oxo-3-[2-(pyrrolidine-1-carbonyl)-benzoylamino]-azetidin-2-yl}-propionic acid 

Relevant academic research and scientific papers

Enantioselective synthesis of loracarbef from sodium erythorbate

Sodium erythorbate (7) has been converted to loracarbef (1). Oxidation of sodium erythorbate to D erythronolactone (8) followed by selective monotosylation and treatment with sodium ethoxide provided ethyl (2S,3R) 4 hydroxy 2.3 epoxybutyrate (10). Swern oxidation of this epoxide into the aldehyde (11), imine formation with tert-butylglycinate and an enantioselective Staudinger reaction with phthalimidoacetyl chloride afforded the (3S,4S)-cis-β-lactam (13). Appropriate functional group manipulations followed by a Dieckmann condensation, chlorination, and protecting group removals gave the enantiomerically pure nucleus of loracarbef (24).

Scope of phthalimido chemistry I. Extension of utility by conversion to the opcb protecting group

The scope of the phthalimido protecting group (PhthN-) is extended by reaction with pyrrolidine. The resulting o-pyrrolidinocarbonylbenzamide ("OPCB-") represents a base/nucleophile stable derivative of the parent, which reverts to the imide form upon treatment with acid. This methodology allows utilization of this protecting group (as the OPCB form in synthetic sequences requiring basic/nucleophilic reaction conditions.