Cesium carbonate → Ethyl 2-[(5-chloropyridin-2-yl)oxy]-2-methylpropanoate

HRID 1394557Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.Br[C:10]([CH3:17])([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH3:16][C:10]([O:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=1)([CH3:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 5-chloro-2-hydroxypyridine (5.0 g, 39 mmol), ethyl 2-bromoisobutyrate (5.7 mL, 39 mmol) and cesium carbonate (25 g, 77 mmol) in 50 mL of acetonitrile was heated at 50° C. overnight. The volatile materials were removed by concentrating on a rotary evaporator, and the residue was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic layer was separated and the aqueous layer extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated to dryness, and the residue was purified by flash column chromatography on silica gel eluted with 5% ethyl acetate in hexane to give the title compound. 1H NMR (500 MHz, CD3OD): δ 7.99 (d, m), 7.67 (dd, 1H), 6.68 (d, 1H), 4.13 (q, 2H), 1.64 (s, 6H), 1.14 (t, 3H). LC-MS: m/e 244 (M+H)+ (3.41 min).

Workup

customThe volatile materials were removed
concentrationby concentrating on a rotary evaporator
customthe residue was partitioned between water (100 mL) and ethyl acetate (100 mL)
customThe organic layer was separated
extractionthe aqueous layer extracted with ethyl acetate (2×100 mL)
dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated to dryness
customthe residue was purified by flash column chromatography on silica gel
washeluted with 5% ethyl acetate in hexane

Sources & evidence

ORD record: ord-ebb5311ff968495397d1b30d5189b4bd
Source dataset: uspto-grants-2008_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07348456B2

Reaction notes

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