Diethyl Malonate → 3-(4-Bromophenyl)propionic acid

A mixture of a 60% suspension of sodium hydride in mineral oil (4.8 g, 120 mmol) in N,N-dimethylformamide (50 mL) at about 5° C. was treated with diethyl malonate (36.4 mL, 240 mmol). The mixture was stirred for about 5 minutes, slowly treated with a solution of 4-bromobenzyl bromide (20.0 g, 80 mmol) in N,N-dimethylformamide (20 mL), stirred at room temperature overnight, diluted with water, and extracted with ethyl acetate. The combined organic extracts were dried (MgSO4), filtered, and concentrated under high vacuum. The residue was dissolved in a mixture of acetic acid (46 mL), water (30 mL), and concentrated sulfuric acid (13 mL) and was heated to reflux for 18 hours. The reaction mixture was cooled, concentrated under high vacuum, and diluted with water. The formed crystalline solid was collected by filtration, washed with water and diethyl ether, and was dried under high vacuum to provide the desired product. MS (DCI-NH3): m/z 246, 248 (M+NH4)+.

1. stirringstirred at room temperature overnight
2. extractionextracted with ethyl acetate
3. dry with materialThe combined organic extracts were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated under high vacuum
6. dissolutionThe residue was dissolved in a mixture of acetic acid (46 mL), water (30 mL), and concentrated sulfuric acid (13 mL)
7. temperaturewas heated
8. temperatureto reflux for 18 hours
9. temperatureThe reaction mixture was cooled
10. concentrationconcentrated under high vacuum
11. additiondiluted with water
12. filtrationThe formed crystalline solid was collected by filtration
13. washwashed with water and diethyl ether
14. customwas dried under high vacuum

ORD record

ord-e74f24ea3af94d828c490902685234e8

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468371B2