Sodium Hydroxide → N-[(4-chlorophenyl)-methyl]-2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzamide

Temperature

80 °C

To a stirred solution of 2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzamide (0.13 g, 0.42 mmol) in tetrahydrofuran/benzene (1:1) (6 ml) is added tetrabutylammonium hydrogen sulfate (15.0 mg, 0.04 mmol) followed by the addition of 15% aqueous sodium hydroxide (3.7 ml) at room temperature. A solution of 4-chloro-benzyl bromide (0.087 g, 0.42 mmol) in tetrahydrofuran (1 ml) is slowly added to the solution and the resulting mixture is heated to 80° C. for 45 min. The mixture is cooled to room temperature and extracted with ethyl acetate (3×10 ml). The combined organic layers are washed with water (10 ml), brine (10 ml), dried over anhydrous sodium sulfate and concentrated in vacuo to get crude product, which is purified by flash column chromatography (silica gel, 10% acetone/hexane) to yield N-[(4-chlorophenyl)-methyl]-2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzamide (example 38) (0.04 g, 0.09 mmol, 22%). [M+H]+ 432.2.

1. temperatureThe mixture is cooled to room temperature
2. extractionextracted with ethyl acetate (3×10 ml)
3. washThe combined organic layers are washed with water (10 ml), brine (10 ml)
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. customto get crude product, which
7. customis purified by flash column chromatography (silica gel, 10% acetone/hexane)

ORD record

ord-688dfca2752544d7a09df13384ac6e1f

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108936B2