Sodium Azide → (3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylate

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Reaction Conditions

Reaction Steps

(3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate (20 g, 51.4 mmol) was dissolved in DMF (42.8 ml). Sodium azide (5.68 g, 87 mmol) was added at rt and heated up to 85° C. overnight. LCMS shows a complete conversion. The reaction mixture was cooled to rt, quenched with ice water, extracted with ethyl acetate. Organic phases were combined, washed with water, brine, then dried with Na2SO4. After concentration, (3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylate (13 g, 97% yield) was obtained as a yellowish oil and used directly for the next reduction. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.29-7.44 (5 H, m), 5.08-5.22 (2 H, m), 3.94-4.04 (1 H, m), 3.52-3.76 (3 H, m), 3.00-3.15 (1 H, m), 2.29-2.48 (1 H, m), 1.13 (3 H, t, J=7.04 Hz); LCMS (Chromolith RP-18e 2.0×50 mm, 0.8 mL/min, Solvent A: 10% MeOH/water with 0.1% TFA, Solvent B: 90% MeOH/water with 0.1% TFA, gradient with 0-100% B over 4 minutes) retention time: 3.41 min; MS (ES+) m/z: 261.0 (M+H+);

Provenance & Evidence