Cesium carbonate → 3-[4-(3-Bromo-5-methyl-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester

HRID 1822278Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Br:9])[CH:3]=1.[CH3:10][O:11][C:12](=[O:23])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=1[CH3:22].CC(C)(C(=O)CC(=O)C(C)(C)C)C.C([O-])([O-])=O.[Cs+].[Cs+]>CN1C(=O)CCC1.CCOCC.Cl[Cu]>[CH3:10][O:11][C:12](=[O:23])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:2]2[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Br:9])[CH:3]=2)=[CH:17][C:16]=1[CH3:22]

Participants

Conditions

Temperature: 120 °C

Procedure

The mixture of 1,3-dibromo-5-methyl-benzene (15 g, 0.06 mol), 3-(4-hydroxy-2-methyl-phenyl)-propionic acid methyl ester (3.9 g, 0.02 mol), CuCl (1 g, 0.01 mol), 2,2,6,6-tetramethyl-heptane-3,5-dione (0.92 g, 0.005 mol) and Cs2CO3 (7.8 g, 0.024 mol) in 40 mL of dry NMP is heated to 120° C. for overnight. The mixture is cooled to rt and diluted with Et2O and filtered through a pad of celite. Organic layer is washed with 1N HCl, H2O and brine, and then dried over Na2SO4, filtered and concentrated. Crude material is purified by chromatography (hexanes/acetone=20:1) to afford the title compound (59%) as a yellow oil. Rf=0.29 (20/1 hexanes/acetone). 1H NMR (400 MHz, CDCl3).

Workup

temperatureThe mixture is cooled to rt
filtrationfiltered through a pad of celite
washOrganic layer is washed with 1N HCl, H2O and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customCrude material is purified by chromatography (hexanes/acetone=20:1)

Sources & evidence

ORD record: ord-295c7ac83b8344d78fa2c85961396096
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608639B2

Reaction notes

Loading…