Sodium hydride → 6-Methyl-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine

HRID 1913432Notes

Reaction equation

I[C:2]1[C:7]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:5]=[C:4]([CH3:12])[N:3]=1.[H-].[Na+]>CN(C=O)C.[O-]S([O-])(=O)=O.[Cu+2]>[CH3:12][C:4]1[N:3]=[C:2]2[O:11][CH2:10][CH2:9][O:8][C:7]2=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred solution of 2-(2-iodo-6-methylpyridin-3-yloxy)ethanol (350 g, 1.25 mol) in anhydrous DMF (3.5 L) was added NaH (60 g, 1.5 mol), Cu (33.7 g, 0.53 mol) and CuSO4 (100 g, 0.63 mol) at 0° C. After the addition, the mixture was stirred at 100° C. overnight. After cooling, the solvent was removed in vacuo and the residue was diluted with water (1.5 L). The aqueous solution was extracted with CH2Cl2 (3×350 mL). The combined organic layers were washed with brine (2×100 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified via column chromatography (silica gel, EtOAc/petroleum ether 1:20) to yield 6-methyl-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (30.0 g, 16%) as a yellow oil.

Workup

additionAfter the addition
temperatureAfter cooling
customthe solvent was removed in vacuo
additionthe residue was diluted with water (1.5 L)
extractionThe aqueous solution was extracted with CH2Cl2 (3×350 mL)
washThe combined organic layers were washed with brine (2×100 mL)
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated
customThe residue was purified via column chromatography (silica gel, EtOAc/petroleum ether 1:20)

Sources & evidence

ORD record: ord-0bcda9c1a9c4405ba511c9d962c19165
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609680B2

Reaction notes

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