Cyclobutanol → 4-(5-Chloro-2-methoxyphenyl)-2-(cyclobutyloxy)pyridine

HRID 46383Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=2[O:15][CH3:16])[CH:5]=[CH:4][N:3]=1.[CH:17]1([OH:21])[CH2:20][CH2:19][CH2:18]1.CC(C)([O-])C.[K+]>O1CCOCC1>[Cl:14][C:12]1[CH:11]=[CH:10][C:9]([O:15][CH3:16])=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([O:21][CH:17]3[CH2:20][CH2:19][CH2:18]3)[CH:7]=2)[CH:13]=1

Participants

Conditions

Temperature: 101 °C

Procedure

2-Chloro-4-(5-chloro-2-methoxyphenyl)pyridine (Preparation 864, 150 mg, 0.00059 mol) and cyclobutanol (76.6 mg, 0.00106 mol) were dissolved in 1,4-dioxane (2 mL). Potassium tert-butoxide (132 mg, 0.00118 mol) was added and the solution stirred at 101° C. for 15 hours. The reaction was partitioned between ethyl acetate (15 mL) and a 10% aqueous solution of citric acid (10 mL). The organic layer was washed with water (10 mL) followed by a saturated aqueous sodium chloride solution (10 mL). The organics were dried over anhydrous magnesium sulphate, filtered and the solvents removed in vacuo to give a yellow oil (195 mg). The material was purified using an ISCO™ companion (12 g column, eluting with 100% heptane to 7:3 heptane/ethyl acetate). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a colourless oil (84 mg).

Workup

customThe reaction was partitioned between ethyl acetate (15 mL)
washThe organic layer was washed with water (10 mL)
dry with materialThe organics were dried over anhydrous magnesium sulphate
filtrationfiltered
customthe solvents removed in vacuo

Sources & evidence

ORD record: ord-e3bba557739f48d0932d39d44ee1c412
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541588B2

Reaction notes

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