Benzyl chloroformate → Methyl 4-(4-(chloromethyl)-5-methyloxazol-2-yl)benzoate

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Reaction Conditions

Reaction Steps

4-(Benzyloxycarbonylamino)methyl)benzoic acid (30). Benzyl chloroformate (10.3 mL, 72.7 mmol) and 2 M NaOH solution (33 mL, 66 mmol) were simultaneously added dropwise to a stirred solution of 4-aminomethylbenzoic acid (29) (10.0 g, 66.2 mmol) in 2 M NaOH solution (33 mL) and THF (30 mL) at 0° C. The mixture was stirred at 20° C. for 16 h, then the organic solvent was evaporated and the residue acidified with 2 M HCl until the pH of the mixture was 2-3. The precipitate was filtered, washed with water (250 mL), washed with EtOH (50 mL), and finally washed with Et2O (100 mL). The solid was dried under vacuum to give acid 2 (16.43 g, 87%) as a white powder: mp 190-192° C. [lit. (Loge et. al., J. Enzyme Inhibit. Med. Chem. 2002, 17, 381-390) mp (toluene) 194-195° C.; 1H NMR δ 7.85 (br d, 2 H, H-2, H-6), 7.82 (br t, J=6.1Hz, 1 H, NHCO2), 7.30-7.40 (m, 5 H, H-2′, H-3′, H-4′, H-5′, H-6′), 7.27 (br d, J=8.2Hz, 2 H, H-3, H-5), 5.05 (s, 2H, OCH2), 4.24 (d, J=6.1Hz, 2 H, CH2N).

Provenance & Evidence