Cyclopropanemethanol → 6-(Cyclopropylmethoxy)-5-(3-fluorooxetan-3-yl)pyridine-2-carboxylic acid

HRID 625004Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1([F:15])[CH2:14][O:13][CH2:12]1.[CH:16]1([CH2:19][OH:20])[CH2:18][CH2:17]1.CC([O-])(C)C.[Na+]>CN(C=O)C.C1COCC1>[CH:16]1([CH2:19][O:20][C:2]2[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=2[C:11]2([F:15])[CH2:14][O:13][CH2:12]2)[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 50 °C

Procedure

6-Chloro-5-(3-fluorooxetan-3-yl)pyridine-2-carboxylic acid (Example 134 e, 44 mg, 190 μmol) and cyclopropylmethanol (CAN 2516-33-8, 17.8 mg, 20.0 μL, 247 μmol) were dissolved in DMF (1.32 mL). A solution of sodium 2-methylpropan-2-olate (42.0 mg, 437 μmol) in THF (800 μL) was added and the mixture was heated to 50° C. for 3 h and for additional 3 h to 70° C. After cooling to ambient temperature, the reaction mixture was poured onto ice/0.1 N HCl (25 mL) and extracted with EtOAc (2×25 mL). The combined extracts were washed with ice/brine (20 mL), dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by thin layer chromatography (2 mm SiO2, dichloromethane/MeOH 19:1, elution with EtOAc) to give the title compound (11 mg, 22 mg) as colorless oil, MS (ESI) m/e=268.2 [MH+].

Workup

temperatureAfter cooling to ambient temperature
additionthe reaction mixture was poured onto ice/0.1 N HCl (25 mL)
extractionextracted with EtOAc (2×25 mL)
washThe combined extracts were washed with ice/brine (20 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated to dryness
customThe residue was purified by thin layer chromatography (2 mm SiO2, dichloromethane/MeOH 19:1, elution with EtOAc)

Sources & evidence

ORD record: ord-12df0d29d61c4becad12ccf6baee29d9
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303012B2

Reaction notes

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