Methyl iodide → 2-(3-Bromophenyl)propanoic acid

Temperature

-78 °C

A solution of LDA in THF/n-heptane/ethylbenzene (1.8M, 23.25 mL, 41.85 mmol) is cooled down to −78° C. and added a solution of 3-bromophenylacetic acid [3 g, 13.95 mmol, Intermediate (68)] in THF (7 mL) dropwise over 15 minutes. The mixture is stirred for 1 h at −78° C. and treated dropwise with methyl iodide (6.34 g, 44.64 mmol) over 15 minutes. The reaction mixture is warmed up to room temperature and after stirring overnight, the mixture is quenched with 2N hydrochloric acid and concentrated to remove THF. The residue is diluted with ether, washed twice with 2 N hydrochloric acid (20 mL) and extracted twice with 10% sodium hydroxide (20 mL). The combined sodium hydroxide extracts are acidified with 6 N hydrochloric acid to pH=1 and extracted three times with ether (50 mL). Combined organic extracts are washed with brine, dried over sodium sulfate and concentrated to obtain 2-(3-bromo-phenyl)-propionic acid [3 g, 100%, Intermediate (69)] as a solid, which is used without further purification. LC/MS: 229 (M+H).

1. temperatureThe reaction mixture is warmed up to room temperature
2. stirringafter stirring overnight
3. customthe mixture is quenched with 2N hydrochloric acid
4. concentrationconcentrated
5. customto remove THF
6. additionThe residue is diluted with ether
7. washwashed twice with 2 N hydrochloric acid (20 mL)
8. extractionextracted twice with 10% sodium hydroxide (20 mL)
9. extractionextracted three times with ether (50 mL)
10. washCombined organic extracts are washed with brine
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated

ORD record

ord-a261cc4345474c57aa167b3464509409

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08193183B2