4-Toluenesulfonyl chloride → (S)-1-Benzyl-3-[(P-tolylsulfonyl)oxy]pyrrolidine

Temperature

0 °C

To a stirred solution of (S)-1-benzyl-3-pyrrolidinol (44.3 g, 0.25 mol) and DABCO (33.7 g, 0.3 mol) in MTBE (250 mL) under an atmosphere of nitrogen at 0° C., was added p-toluenesulfonyl chloride (52.4 g, 0.275 mol) portionwise over 20 minutes. The reaction mixture was stirred at 0° C. for 1 hour. The ice bath was removed and the mixture was stirred at ambient temperature overnight (20±5 hours). EtOAc (100 mL) was added, followed by saturated aqueous sodium bicarbonate solution (250 mL). The resulting mixture was stirred at ambient temperature for 1 hour. 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 NaCl solution (250 mL); and then dried over sodium sulfate (80 g). The sodium sulfate was filtered off and washed with EtOAc (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 hours)
3. additionEtOAc (100 mL) was added
4. stirringThe resulting mixture was stirred at ambient temperature for 1 hour
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 EtOAc (20 mL)
10. customthe solvent was removed in vacuo

ORD record

ord-c4c540c672aa4fc98c4d48f5c60ca3df

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07524880B2