3-Hydroxypyridine → 3-(2-(Tetrahydropyran-2-yloxy)ethoxy)pyridine

HRID 1421022Notes

Reaction equation

[H-].[Na+].[OH:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1.Br[CH2:11][CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1>CN(C=O)C.O>[O:15]1[CH2:16][CH2:17][CH2:18][CH2:19][CH:14]1[O:13][CH2:12][CH2:11][O:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Sodium hydride (1.02 g of a 50% suspension in mineral oil, 42 mmol) was added to a solution of 3-hydroxypyridine (2.01 g, 21 mmol) in DMF (50 ml) and the mixture stirred for 30 minutes. 2-(2-Bromoethoxy)tetrahydropyran (4.0 g, 19 mmol), (J. Am. Chem. Soc. 1948, 70, 4187), was added and the mixture heated at 100° C. for 3 hours and then stirred at ambient temperature for 18 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed with water, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol mixtures (100/0 increasing to 97/3) to give 3-(2-(tetrahydropyran-2-yloxy)ethoxy)pyridine (2.28 g, 48%).

Workup

stirringstirred at ambient temperature for 18 hours
extractionextracted with ethyl acetate
washThe combined extracts were washed with water
dry with materialdried (MgSO4)
customthe solvent removed by evaporation
customThe residue was purified by column chromatography
washeluting with methylene chloride/methanol mixtures (100/0 increasing to 97/3)

Sources & evidence

ORD record: ord-d6fb13ba821445cc8b0a0ba948043394
Source dataset: uspto-grants-2000_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06071921

Reaction notes

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