Dimethylformamide → 3-Ethyl-4-hydroxy-5-methyl-benzoic acid benzyl ester

HRID 2040802Notes

Reaction equation

[CH2:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:13])[C:11]=1[OH:12])[C:6]([OH:8])=[O:7])[CH3:2].CN(C=O)C.[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O>[CH2:19]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([CH3:13])[C:11]([OH:12])=[C:3]([CH2:1][CH3:2])[CH:4]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-ethyl-4-hydroxy-5-methyl-benzoic acid (80.3 g, 0.446 mol) is DMF (500 mL), KHCO3 (53.5 g, 0.535 mol) followed by benzylbromide (114.3 g, 0.668 mol) is added. The mixture is stirred at 50° C. for 18 h before it is cooled to rt, diluted with water (250 mL), and extracted with TBME (2×250 mL). The org. extracts are washed with water, and then concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 19:1 to 9:1 to give 3-ethyl-4-hydroxy-5-methyl-benzoic acid benzyl ester (108.5 g) as a beige solid; 1H NMR (CDCl3): δ 1.28 (t, J=7.5 Hz, 3 H), 2.30 (s, 3 H), 2.68 (q, J=7.8 Hz, 2 H), 5.24 (s, 1 H), 5.37 (s, 2 H), 7.33-7.45 (m, 3 H), 7.45-7.50 (m, 2 H), 7.77 (s, 1 H), 7.79 (s, 1 H).

Workup

additionis added
temperatureis cooled to rt
extractionextracted with TBME (2×250 mL)
washextracts are washed with water
concentrationconcentrated
customThe crude product is purified by CC on silica gel eluting with heptane:EA 19:1 to 9:1

Sources & evidence

ORD record: ord-edce014358614799a18e31045f5fa7fe
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580824B2

Reaction notes

Loading…