4-Methoxyphenylacetic Acid → 2-(4-Methoxyphenyl)-4-(3-methoxyphenyl)butyric acid

HRID 1416978Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[Li]CCCC.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27]Br)[CH:23]=[CH:24][CH:25]=1>C1COCC1.CCCCCC>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH2:27][CH2:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH3:18])[CH:21]=2)[C:10]([OH:12])=[O:11])=[CH:7][CH:8]=1

Participants

Conditions

Temperature: -70 °C

Procedure

4-Methoxyphenylacetic acid (50.68 g, 305 mmol) was dissolved in 1.4 L of THF and cooled to -70° C. under a nitrogen atmosphere. 400 mL of 1.6M (640.5 mmol) of n-BuLi in hexane was slowly added. 72.1 g (335.5 mmol) of 2-(3-methoxyphenyl)ethylbromide in 400 mL of THF was slowly added and the reaction allowed to proceed for 1.5 hours. The reaction was allowed to warm to ambient temperature. The reaction was quenched with 500 mL of 0.5N NaOH and heated to 50° C. for one hour and cooled to ambient temperature. The reaction mixture was extracted three times with ether, the aqueous layer was acidified with 150 mL of 5N HCl and extracted twice with CHCl3. The CHCl3 extract was washed twice with brine, dried with Na2SO4, and evaporated to a yellow solid. This yielded 78.2 g of the title compound.

Workup

temperatureto warm to ambient temperature
customThe reaction was quenched with 500 mL of 0.5N NaOH
temperatureheated to 50° C. for one hour
temperaturecooled to ambient temperature
extractionThe reaction mixture was extracted three times with ether
extractionextracted twice with CHCl3
extractionThe CHCl3 extract
washwas washed twice with brine
dry with materialdried with Na2SO4
customevaporated to a yellow solid

Sources & evidence

ORD record: ord-0ba4f4c4e7cc462b9115bff6274f4b4a
Source dataset: uspto-grants-1999_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05916916

Reaction notes

Loading…