反应详情

The methods of the invention are outlined in the following preparation scheme. All compounds were characterized by high-field NMR (1H, 13C, 11B) and by IR; new compounds were also characterized by combustion analysis (C,H,N). Bracketed numerals refer to like numbered reactions or reaction products in the drawing of the specification. In the first step 4-boronobenzaledhyde (2) was prepared in 93% yield from the ethylene glycol acetal of 4-bromobenzaldehyde (1) by a Grignard reaction with tributyl borate (10B enriched material may be used). The hydrolysis must be done at low temperature to produce (2) in high efficiency. Direct reaction of aldehyde (2) with uric or hippuric acid by the conventional procedure is not possible, as all attempts resulted in B-C cleavage. Therefore, the boronic acid group was protected by esterification with diethanolamine giving compound (3). Since the B-C cleavage described above probably resulted from reaction of the aryl boronic acid and ester with acetic anhydride, 2-phenyl-2-oxazolin-5-one was prepared and achieved the preparation of azlactone (4) in 62% yield by refluxing in dioxane. Boiling yellow (4) in 1% KOH.H2O for 15 min produced a colorless solution which, upon acidification, precipitated white N-benzoylamino-4-boronocinnamic acid (5) in 87% yield. The product was the desired Z isomer as evidenced by its vinyl resonance at δ7.44; the undesirable E isomer should resonate a δ6.66, by analogy with its un-boronated analogue, but no E isomer was observed.

1. customas all attempts resulted in B-C cleavage