2,3-Dimethylphenol → Ethyl 4-(2,3-dimethylphenoxy)butyrate

HRID 2175207Notes

Reaction equation

[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].Br[CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)([O-])[O-].[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 2,3-dimethylphenol (12.2 g, 100 mmol), tetrabutylammonium iodide (0.738 g, 1.997 mmol), ethyl 4-bromobutanoate (14.29 mL, 100 mmol), and potassium carbonate (27.6 g, 200 mmol) in THF (100 mL) was heated at 60° C. for 20 h. After this time, the reaction mixture was cooled to room temperature. Once at the prescribed temperature, the reaction mixture was quenched with water (50 mL), and extracted with EtOAc (2×50 mL). The combined organic phases were concentrated, and purified by flash chromatography (0 to 30% EtOAc:hexanes) to afford the title compound (22.5 g, 90% yield) as colorless oil. LCMS, [M+Na]+=259.1. 1H NMR (400 MHz, CDCl3) δ 7.01 (dd, J=8.2, 7.5 Hz, 1H), 6.75 (d, J=7.5 Hz, 1H), 6.67 (d, J=8.2 Hz, 1H), 4.13 (q, J=7.1 Hz, 2H), 3.97 (t, J=6.0 Hz, 2H), 2.52 (t, J=7.4 Hz, 2H), 2.25 (s, 3H), 2.15-2.07 (m, 2H), 2.12 (s, 3H), 1.24 (t, J=7.1 Hz, 3H).

Workup

temperatureAfter this time, the reaction mixture was cooled to room temperature
customOnce at the prescribed temperature, the reaction mixture was quenched with water (50 mL)
extractionextracted with EtOAc (2×50 mL)
concentrationThe combined organic phases were concentrated
custompurified by flash chromatography (0 to 30% EtOAc:hexanes)

Sources & evidence

ORD record: ord-709538b54041452eaf9860e139e4b9c2
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062028B2

Reaction notes

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