Cesium carbonate → 6-(4-Methanesulfonyl-phenoxy)-2-methyl-2,3-dihydro-benzofuran-4-carboxylic acid methyl ester

HRID 1643535Notes

Reaction equation

[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](F)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]([OH:32])[CH:25]=[C:26]2[O:30][CH:29]([CH3:31])[CH2:28][C:27]=12)=[O:21]>CN(C=O)C>[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]([O:32][C:8]2[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)[CH:25]=[C:26]2[O:30][CH:29]([CH3:31])[CH2:28][C:27]=12)=[O:21]

Participants

Conditions

Temperature: 120 °C

Procedure

4-Fluorophenyl methyl sulfone (307 mg, 1.76 mmol) and Cs2CO3 (1.15 g, 3.52 mmol) were added to a solution of 6-hydroxy-2-methyl-2,3-dihydro-benzofuran-4-carboxylic acid methyl ester (1e) (366 mg, 1.76 mmol) in DMF (8 mL). The mixture was heated to 120° C. for 1 hr, cooled to room temperature, quenched with H2O (50 mL) and extracted with EtOAc (2×50 mL). The organic layers were washed with H2O (2×80 mL), dried over MgSO4 and concentrated. The residue was purified by flash column chromatography eluting with 40% EtOAc in hexanes to give a pale brown solid (350 mg, 55% yield). 1H NMR (400 MHz, CDCl3) δ 7.84-7.93 (m, 2 H) 7.18 (d, J=2.02 Hz, 1 H) 7.04-7.14 (m, 2 H) 6.67 (d, J=2.27 Hz, 1 H) 4.94-5.17 (m, 1 H) 3.89 (s, 3 H) 3.68 (dd, J=17.43, 8.84 Hz, 1 H) 3.13 (dd, J=17.43, 7.58 Hz, 1 H) 3.07 (s, 3H) 1.51 (d, J=6.32 Hz, 3 H);); LCMS for C18H18O6S m/z 363.0 (M+H)+.

Workup

temperaturecooled to room temperature
customquenched with H2O (50 mL)
extractionextracted with EtOAc (2×50 mL)
washThe organic layers were washed with H2O (2×80 mL)
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue was purified by flash column chromatography
washeluting with 40% EtOAc in hexanes

Sources & evidence

ORD record: ord-8323b58d20214712940a6f2faf7dc1f5
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119624B2

Reaction notes

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