Hydrochloric Acid → Methyl 5-bromo-6-(2-fluoroethoxyl)pyridine-2-carboxylate

HRID 625019Notes

Reaction equation

CC([O-])(C)C.[Li+].[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C:15]([O:17][CH3:18])=[O:16])=[N:12][C:13]=1Cl.[F:19][CH2:20][CH2:21][OH:22].Cl>CN(C=O)C.O>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C:15]([O:17][CH3:18])=[O:16])=[N:12][C:13]=1[O:22][CH2:21][CH2:20][F:19]

Participants

Conditions

Temperature: 70 °C

Procedure

Lithium 2-methylpropan-2-olate (4.17 mL, 9.18 mmol) was added within 30 minutes at ambient temperature to a solution of methyl 5-bromo-6-chloro-pyridine-2-carboxylate (CAN 1214353-79-3, 1 g, 3.99 mmol) and 2-fluoroethanol (CAN 371-62-0, 332 mg, 300 μL, 5.19 mmol) in DMF (6.67 mL). The reaction mixture was heated to 70° C. and stirred for 6 h. After cooling to ambient temperature, water (5 mL) and 2N HCl (5 mL) were added. The mixture was poured onto ice/brine (50 mL) and extracted with EtOAc (2×50 mL). The combined extracts were washed with ice/brine (50 mL), dried over Na2SO4, filtered and evaporated to dryness. The crude product was purified by flash-chromatography (50 g SiO2, heptane/0-30% EtOAc in 120 min.) to give the title compound (132 mg, 12%) as light brown solid, MS (ESI) m/e=278.0 [MH+].

Workup

temperatureAfter cooling to ambient temperature
additionThe mixture was poured onto ice/brine (50 mL)
extractionextracted with EtOAc (2×50 mL)
washThe combined extracts were washed with ice/brine (50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated to dryness
customThe crude product was purified by flash-chromatography (50 g SiO2, heptane/0-30% EtOAc in 120 min.)

Sources & evidence

ORD record: ord-5a3a66ebd45a420ca033eef0e7ee931a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303012B2

Reaction notes

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