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

Temperatur

85 °C

(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+);

1. temperatureThe reaction mixture was cooled to rt
2. customquenched with ice water
3. extractionextracted with ethyl acetate
4. washwashed with water, brine
5. dry with materialdried with Na2SO4
6. concentrationAfter concentration

ORD-Eintrag

ord-c47ce84c10c64a5bb131aaa3771b5990

Quelldatensatz

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08987268B2