Methyl iodide → HCID 15128679, compound

Temperature

-78 °C

To 25 mmole (3 equiv.) of a freshly prepared solution of lithium diisopropylamide in tetrahydrofuran (prepared by addition of 9.6 ml of a 2.6 M solution of n-butyllithium in hexane to 7.5 ml of freshly distilled diisopropylamine in 50 ml of tetrahydrofuran at -78° C.) was added 3.0 g of 7-chloro-1,3,4,5-tetrahydro-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one (8.35 mmole). After stirring at -78° C. for 1.5 hours, 1.5 ml of hexamethylphosphoric triamide was added along with 5.9 g of iodomethane (41.7 mmole, 5 equiv.). The reaction mixture was stirred at -78° C. to 20° C. for 6 hours, then quenched with 50 ml of 1N hydrochloric acid. The stirring was continued at 50° C. for 30 minutes. The layers were separated. The aqueous layer was extracted with two 50 ml portions of ethyl acetate. The combined organic layer was washed with two 20 ml portions of saturated sodium bicarbonate, 20 ml of water then dried (magnesium sulfate) and concentrated. The residue was purified on a silica gel column. Elution with 25% ethyl acetate/hexanes gave 1.4 g of 7-chloro-1,3,4,5-tetrahydro-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-3-methyl-2H-1-benzazepin-2-one as a white solid.

1. stirringThe reaction mixture was stirred at -78° C. to 20° C. for 6 hours
2. customquenched with 50 ml of 1N hydrochloric acid
3. waitThe stirring was continued at 50° C. for 30 minutes
4. customThe layers were separated
5. extractionThe aqueous layer was extracted with two 50 ml portions of ethyl acetate
6. washThe combined organic layer was washed with two 20 ml portions of saturated sodium bicarbonate, 20 ml of water
7. dry with materialthen dried (magnesium sulfate)
8. concentrationconcentrated
9. customThe residue was purified on a silica gel column
10. washElution with 25% ethyl acetate/hexanes

ORD record

ord-4e8a5988cd5d42ffa2ec739ccdf9f287

Source dataset

uspto-grants-1988_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04752645