Hydrochloric Acid → Hydrochloric Acid

(R)-3-(S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester (2.0 g, 7.2 mmol) was dissolved in anhydrous DMF (10 mL, 100 mmol). Lithium hydride (86 mg, 11 mmol) was added in 3 separate portions. The mixture was stirred at room temperature for 15 minutes. Into the mixture was added 3,5-dichlorofluorobenzene (1.7 mL, 14 mmol), and the resultant mixture stirred at room temperature for 15 minutes. The mixture was then stirred at 70° C. overnight. The mixture was cooled to room temperature, and EtOAc (80 mL) and 1M HCl (50 mL) were added. After mixing, the phases were separated and the organic layer was washed with diluted aqueous NaCl (1×50 mL), dried over Na2SO4, and concentrated to dryness to yield 3.5 g of crude product. Into the crude product was added 25 mL cold HCl in an EtOH/EtOAc solution and stirred at room temperature for 3 hours. Most of the solvent was removed by rotary evaporation, EtOAc was added (50 mL) and most of the solvent was removed again. Recrystallization and reslurry from EtOAc (20 mL) gave (R)-3-[(S)-(3,5-dichlorophenoxy)phenylmethyl]pyrrolidine as an HCl salt (2 g, ˜99% purity).

1. customseparate portions
2. stirringThe mixture was then stirred at 70° C. overnight
3. temperatureThe mixture was cooled to room temperature
4. additionAfter mixing
5. customthe phases were separated
6. washthe organic layer was washed with diluted aqueous NaCl (1×50 mL)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated to dryness
9. customto yield 3.5 g of crude product
10. stirringstirred at room temperature for 3 hours
11. customMost of the solvent was removed by rotary evaporation, EtOAc
12. additionwas added (50 mL)
13. custommost of the solvent was removed again
14. customRecrystallization

ORDレコード

ord-d52795f6323349819b8a0b39a8c75f33

出典データセット

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07888386B2