Tetrahydrofuran → 2-Oxo-2,3-dihydro-1,3-benzoxazole-6-carbaldehyde

HRID 2355985Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.C([Li])CCC.C([Li])(CC)C.[O:22]1CCC[CH2:23]1>CN(C)C=O>[O:9]=[C:7]1[NH:6][C:5]2[CH:10]=[CH:11][C:2]([CH:23]=[O:22])=[CH:3][C:4]=2[O:8]1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 6-bromo-3H-benzooxazol-2-one (0.9236 g, 4.31 micromoles) in anhydrous tetrahydrofuran (25 mL) and dimethylformamide (3 mL) under nitrogen was cooled to −78° C. before addition of n-butyllithium (2.5M in hexane) (3.8 mL, 2.2 equiv). After stirring for 10 min at −78° C., 24 mL of sec-butyllithium (1.4 M in cyclohexane, 8 equiv) was added. The reaction was stirred while slowly warming to −40° C. When this temperature was reached, the reaction was quenched by addition of methanol. The reaction mixture was concentrated in vacuo and water was added. The aqueous layer was acidified with 1N HCl (ca. pH 5) and extracted with ethyl acetate (3×50 mL), dried over sodium sulfate, filtered and concentrated to give the product, 0.6402 g (91%). MS (ESI) 164 (MH)+. 1H NMR (400 MHz, DMSO-d6) δ 9.90 (1H, s), 7.79 (1H, d, J=8.0 Hz), 7.74 (1H, s), 7.28 (1H, d, J=8.0 Hz).

Workup

stirringThe reaction was stirred
temperaturewhile slowly warming to −40° C
customthe reaction was quenched by addition of methanol
concentrationThe reaction mixture was concentrated in vacuo and water
additionwas added
extractionextracted with ethyl acetate (3×50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give the product, 0.6402 g (91%)

Sources & evidence

ORD record: ord-c26358fb3d124f0c9b725033865dfe35
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754732B2

Reaction notes

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