4-Toluenesulfonyl chloride → (3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate

(3R,4S)-benzyl 3-hydroxy-4-methylpyrrolidine-1-carboxylate (19.6 g, 83 mmol) was dissolved in pyridine (83 ml). To the above solution, Ts-Cl (22.2 g, 117 mmol) was added in portions at rt. After overnight stirring, the reaction mixture was concentrated in vacuo to remove pyridine. The residue was quenched with ice water (200 mL), extracted with ethyl acetate (3×150 mL). The combined ethyl acetate phase was washed with water, 1N HCl, water and sat. NaHCO3, then dried with Na2SO4. After concentration, (3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate (30 g, 92% yield) was obtained as light yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.76-7.83 (2 H, m), 7.30-7.40 (7 H, m), 5.11 (2 H, s), 4.57-4.64 (1 H, m), 3.56-3.73 (2 H, m), 3.38-3.54 (1 H, m), 3.08-3.19 (1 H, m), 2.33-2.55 (4 H, m), 0.97 (3 H, dd, J=14.86, 7.15 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: 3.60 min; MS (ES+) m/z: 390 (M+H+);

1. concentrationthe reaction mixture was concentrated in vacuo
2. customto remove pyridine
3. customThe residue was quenched with ice water (200 mL)
4. extractionextracted with ethyl acetate (3×150 mL)
5. washThe combined ethyl acetate phase was washed with water, 1N HCl, water and sat. NaHCO3
6. dry with materialdried with Na2SO4
7. concentrationAfter concentration

ORD record

ord-206375c42f5f4628adcc56cb5a42fa94

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2