Lithium Hydroxide → (3S,4R)-4-(2,4-difluorophenyl)-1-methylpyrrolidine-3-carboxylic acid

To a solution of methyl (3S,4R)-4-(2,4-difluorophenyl)-1-methylpyrrolidine-3-carboxylate, from preparation 37 (800 mg, 3.13 mmol) in tetrahydrofuran (10 mL) was added lithium hydroxide (150 mg, 6.27 mmol) at room temperature. The reaction mixture was stirred for 2 hours and the solvent concentrated in vacuo. The crude residue was dissolved in water (20 mL) and partitioned with ethyl acetate (2×20 mL). The phases were separated and the aqueous phase was acidified using 2M hydrochloric acid solution (3.13 mL). The aqueous phase was evaporated and the residue was azeotroped with toluene (6×20 mL) to afford an oily residue (1000 mg) which was used without further purification in the subsequent step.

1. concentrationthe solvent concentrated in vacuo
2. dissolutionThe crude residue was dissolved in water (20 mL)
3. custompartitioned with ethyl acetate (2×20 mL)
4. customThe phases were separated
5. customThe aqueous phase was evaporated
6. customthe residue was azeotroped with toluene (6×20 mL)

ORD record

ord-41bfea08116b4098a91a28f5ad660adf

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07649002B2