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

HRID 1487301Notes

Reaction equation

HRID 1487301 reaction equation
[OH:1][C@@H:2]1[C@@H:6]([CH3:7])[CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3]1.[S:18](Cl)([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19]>N1C=CC=CC=1>[CH3:7][C@@H:6]1[C@@H:2]([O:1][S:18]([C:21]2[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH2:3][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:5]1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 58277753benzyl (3R,4S)-3-hydroxy-4-methylpyrrolidine-1-carboxylate

Product 1

HCID 86707891(3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylateYield 92.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

(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 (2H, m), 7.30-7.40 (7H, m), 5.11 (2H, s), 4.57-4.64 (1H, m), 3.56-3.73 (2H, m), 3.38-3.54 (1H, m), 3.08-3.19 (1H, m), 2.33-2.55 (4H, m), 0.97 (3H, 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+).

Workup

  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

Sources & evidence

ORD record
ord-95ffff329ea94338ae11a981d3d1d20a
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

Loading…