Oxalyl chloride → 9H-fluoren-9-ylmethyl(2-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl)carbamate

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Reaction Steps

Oxalyl chloride (1.12 g, 8.83 mmol) in DCM (5 mL) was added slowly to a stirred solution of 2-(tert-butyl-dimethyl-silanyloxy)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (Step 1) (1.30 g, 2.94 mmol) in DCM (25 ml) and DMF (50 μl ) at 0° C. After 3 hrs at ambient temperature, gas evolution had subsided and the reaction mixture was concentrated in vacuo. THF (20 mL) and DIPEA (0.57 g, 4.4 mmol) were added, followed by the addition of 2-amino-4-methylthiazole (0.403 g, 3.53 mmol) in DCM (5 mL). The reaction mixture was kept at ambient temperature for 3 hrs. Water (0.5 mL) was added and the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluting with a gradient consisting of 0-40% EtOAc in heptane) to give the title compound as a colorless oil (0.10 g). 1H NMR (500 MHz, CDCl3) δ 9.60 (br s, 1H), 7.75 (d, 2H), 7.57 (d, 2H), 7.39 (t, 2H), 7.30 (t, 2H), 6.56 (s, 1H), 5.19 (br s, 1H), 4.41 (t, 1H), 4.37 (d, 2H), 4.21 (t, 1H), 3.66 (m, 1H), 3.49 (m, 1H), 2.35 (s, 3H), 0.98 (s, 9H), 0.20 (s, 6H).

Provenance & Evidence