A safe, functional-group-tolerant and high-throughput version of the trimethylaluminium mediated amide bond formation reaction has been developed in a microreactor system; rimonabant and efaproxiral were prepared to illustrate the utility of the method.

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Early scale-up work of a promising reflux inhibitor AZD6906 is described. Two steps of an earlier route were adapted to be performed in continuous flow to avoid issues related to batch procedures, resulting in a robust method with reduced cost of goods and improved product quality. Toxic and reactive reagents and starting materials could be handled in a flow regime, thereby allowing safer and more convenient reaction optimization and production.

Reaction of the bromosugars 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (1), methyl 2,3-anhydro-6-bromo-6-deoxy-alpha-D-allopyranoside (2), and methyl 2,3-anhydro-4-O-benzoyl-6-bromo-6-deoxy-alpha-D-allopyranoside (3) with the allylic sulfides and sulfones 4-9 in the presence of hexabutyldistannane under photolytic conditions gave the corresponding alpha-C-allyl galactosides 10-12 and the 6-C-allylated epoxysugars 13, 15, and 16 in 61-90% yield.

A synthesis of N-Boc (2R)-1,4-oxazepane-2-carboxylic acid 1 has been developed in 39% yield over seven steps starting from methyl (2R)-glycidate 2. The key step was a lipase-catalyzed regioselective lactamization of amino diester 5 into seven-membered lactam 6. The transformation was performed using SpinChem rotating flow cell technology which simplified the work up and the recycling of the enzyme. Subsequent N-Boc protection followed by chemoselective borane reduction of the lactam moiety afforded 4-tert-butyl 2-methyl (2R)-1,4-oxazepane-2,4-dicarboxylate 8. Finally, hydrolysis mediated by LiBr/Et 3 N in wet acetonitrile yielded the title compound (2R)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid 1.