Hydrochloric Acid → ethyl 6-hydroxy-8-methoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855105Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:6]=[C:7]2[C:12]=1[O:11][CH:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:8]2.[OH:31]O.[OH-].[Na+].Cl>C1COCC1.O>[OH:31][C:5]1[CH:6]=[C:7]2[C:12](=[C:3]([O:2][CH3:1])[CH:4]=1)[O:11][CH:10]([C:13]([F:14])([F:16])[F:15])[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:8]2

Participants

Conditions

Temperature: 0 °C

Procedure

The ethyl 8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate (0.21 g, 0.49 mmole) was dissolved in THF (3 mL) and cooled to 0° C. (ice bath). Hydrogen peroxide (0.25 g, 0.074 mmole) followed by 2.5N sodium hydroxide (0.20 mL) was added dropwise and the resulting solution was stirred for 3 hours. The contents were poured into water (20 mL) and acidified using 2.4 N HCl to pH around 1 and extracted with EtOAc (2×20 mL). The combined extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil which was subject to flash chromatography (silica gel) and eluted with 0-35% EtOAc/ hexanes to give yellow solid (0.1 g, 65%). LCMS m/z 319.0 (M+H). 1H NMR (CDCl3/400 MHz) 7.58 (s, 1H), 6.50 (s, 1H), 6.29 (s, 1H), 5.66 (q, 1H, J=7.0 Hz), 4.29 (m, 2H), 3.86 (s, 3H), 1.32 (m, 3H).

Workup

additionwas added dropwise
extractionextracted with EtOAc (2×20 mL)
washThe combined extracts were washed with brine (20 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customto give a yellow oil which
washeluted with 0-35% EtOAc/ hexanes

Sources & evidence

ORD record: ord-0f57f2b7fa854c6196121253bb90a00d
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07259266B2

Reaction notes

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