4-Toluenesulfonyl chloride → (3S)-1-Benzylpyrrolidin-3-yl 4-methylbenzene-1-sulfonate

Temperature

0 °C

To a stirred solution of (S)-1-benzyl-3-pyrrolidinol (44.3 g, 0.25 mol) and 1,4-diazabicyclo[2.2.2]octane (33.7 g, 0.3 mol) in 250 mL of tert-butyl methyl ether under an atmosphere of nitrogen at 0° C., was added p-toluenesulfonyl chloride (52.4 g, 0.275 mol) portion-wise over 20 min. The reaction mixture was stirred at 0° C. for 1 h. The ice bath was removed and the mixture was stirred at ambient temperature overnight (20±5 h). Ethyl acetate (100 mL) was added, followed by saturated aqueous sodium bicarbonate solution (250 mL). The resulting mixture was stirred at ambient temperature for 1 h. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate solution (250 mL); saturated aqueous ammonium chloride solution (250 mL); saturated aqueous sodium chloride solution (250 mL); and then dried over sodium sulfate (80 g). The sodium sulfate was filtered off and washed with ethyl acetate (20 mL) and the solvent was removed in vacuo to give 78.2 g of the title intermediate as an off-white solid (94% yield; 95% purity by HPLC).

1. customThe ice bath was removed
2. stirringthe mixture was stirred at ambient temperature overnight (20±5 h)
3. additionEthyl acetate (100 mL) was added
4. stirringThe resulting mixture was stirred at ambient temperature for 1 h
5. customThe layers were separated
6. washthe organic layer was washed with saturated aqueous sodium bicarbonate solution (250 mL)
7. dry with materialand then dried over sodium sulfate (80 g)
8. filtrationThe sodium sulfate was filtered off
9. washwashed with ethyl acetate (20 mL)
10. customthe solvent was removed in vacuo

ORD record

ord-7aa463aef3a642d887e3092fbe0294dc

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07183292B2