2-(2-Boc-amino-5-chlorothiazol-4-YL)-2-oxoacetic acid → (2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[(2S)-1-[(4-methoxyphenyl)methoxy]-4-[(2-methylpropan-2-yl)oxy]-1,4-dioxobutan-2-yl]oxyiminoacetic acid

Participants

Reaction Steps

To a solution of (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(aminooxy)succinate (39.7 g, 122 mmol) in Methanol (300 mL) was added a solution of 2-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)-2-oxoacetic acid (Example 21b) (34 g, 111 mmol) at 0° C. Then the mixture was allowed to warm up to rt and stirred for 2 h. LCMS indicated completion of the reaction and the product as a mixture of Z/E isomer (19:1). The reaction mixture was concentrated and the residue was purified by reverse phase automatic C18 column chromatography (Combinflash RF, 150 g column, six runs), eluting with Acetonitrile/Water (0-90%) to afford (S,Z)-2-(((4-(tert-butoxy)-1-((4-methoxybenzyl)oxy)-1,4-dioxobutan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)acetic acid (46 g, 74.9 mmol, 67.6% yield) as pale yellow solid. LCMS: (M+H)+: 614.4. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.44 (s, 9 H) 1.55 (s, 9 H) 2.74-2.96 (m, 2 H) 3.78 (s, 3 H) 5.06-5.13 (m, 1 H) 5.17 (s, 2 H) 6.86 (d, J=8.84 Hz, 2 H) 7.32 (d. J=8.59 Hz, 2 H)

Provenance & Evidence