2-Bromopropanedial → (S)-ter-Butyl 1-(5-formylthiazol-2-yl)pyrrolidine-2-carboxylate

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Reaction Steps

To a solution of material from Example 78 (1.075 g, 4.67 mmol) in a mixture of THF (51.3 mL) and acetic acid (8.55 mL) is added sodium acetate (0.46 g, 5.60 mmol), followed by 2-bromomalonaldehyde (0.82 g, 5.13 mmol) and the reaction is stirred at room temp for 2 h. The solvent is removed in vacuo, the residue is partitioned between water and CH2Cl2 and the water layer is extracted with CH2Cl2 (1×20 mL). The organic layers are combined, partitioned with water and treated with solid sodium bicarbonate until the water layer has pH=8. The water layer is extracted with CH2Cl2 (2×25 mL), the organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo, The resulting residue is purified by BIOTAGE® Silica gel chromatography on a Thompson Single Step silica cartridge using an isocratic mixture of 40% ethyl acetate/60% CH2Cl2 to give 945 mg (68.1%) of the title compound as a yellow solid. LC/MS (Condition A): ret. T=3.23 min, (M+Na) 305.14. 1H NMR (400 MHz, chloroform-d) δ ppm 9.69 (1 H, s), 7.89 (1 H, s), 4.49 (1 H, br. s.), 3.36-3.87 (2 H, m), 2.32-2.51 (1 H, m), 2.03-2.29 (3 H, m), 1.46 (9 H, s).

Provenance & Evidence