Sodium Hydroxide → Methyl 4-bromobicyclo(2.2.2)octane-1-carboxylate

To a suspension of 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (11.0 g, 51.8 mmol) in acetone (80 mL) was added aqueous sodium hydroxide solution (1 M, 51.8 mL, 51.8 mmol) and a solution of silver nitrate (8.8 g, 51.9 mol) in water (10 mL). The precipitate formed was collected by filtration, washed with water, acetone and diethyl ether and dried in vacuo at 115° C. for 4 h. The obtained ((4-(methoxycarbonyl)-bicyclo[2.2.2]octane-1-carbonyl)oxy)silver (15.3 g, 47.9 mmol) was suspended in hexane (125 mL), followed by addition of bromine (7.7 g, 48.1 mmol) over 30 min at room temperature. After the addition was completed, the reaction mixture was stirred at room temperature for another 30 min. The reaction mixture was filtered to remove the solid, and the filter cake was washed with hexane (150 mL×4). The combined organic filtrates were washed with saturated aqueous sodium bicarbonate solution (150 mL×2) and brine (200 mL), then dried over magnesium sulfate. Concentration under reduced pressure gave the crude product, which was purified by silica gel column chromatography (5% ethyl acetate in petroleum ether) to afford the title compound (4.2 g, 0.17 mol, 33% yield over two steps). 1H NMR (400 MHz, CDCl3): δ ppm 3.64 (s, 3H), 2.27-2.20 (m, 6H), 1.98-1.94 (m. 6H).

1. customThe precipitate formed
2. filtrationwas collected by filtration
3. washwashed with water, acetone and diethyl ether
4. customdried in vacuo at 115° C. for 4 h
5. additionAfter the addition
6. filtrationThe reaction mixture was filtered
7. customto remove the solid
8. washthe filter cake was washed with hexane (150 mL×4)
9. washThe combined organic filtrates were washed with saturated aqueous sodium bicarbonate solution (150 mL×2) and brine (200 mL)
10. dry with materialdried over magnesium sulfate
11. concentrationConcentration under reduced pressure
12. customgave the crude product, which
13. customwas purified by silica gel column chromatography (5% ethyl acetate in petroleum ether)

ORD record

ord-1b2a2c0460844406846b5e6313bef419

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139534B2