methyl 3-chloro-5-(hydroxymethyl)picolinate synthesis

Yield:1198016-49-7 66%

Reaction Conditions:

with hydrogenchlorideReflux;Cooling with ice;

Steps:

13.a

Preparation 13; 5-Chloro-6-(1-hydroxy-1-methylethyl)-3-pyridinecarbaldehyde (Used to prepare Example 62) (a) Methyl 3-chloro-5-(hydroxymethyl)-2-pyridinecarboxylateHCl (gas) was bubbled through a solution of 3-chloro-5-(hydroxymethyl)-2-pyridinecarbonitrile (for a synthesis see Preparation 4(a)) (400 mg, 2.373 mmol) in MeOH (25 mL) in ice bath. The mixture was refluxed overnight. HCl gas was bubbled through the solution for a few minutes. The mixture was refluxed overnight. HPLC showed starting material and desired compound. HCl gas was bubbled through the solution for a few minutes. The mixture was refluxed for two days. The mixture was concentrated in vacuo and dissolved with DCM. The organic layer was washed with saturated NaHCO₃ solution and brine, dried over Na₂SO₄, filtered and concentrated to give the title compound (332.6 mg, 66%) as brown oil pure enough to be used in the next step.[ES MS] m/z 202 (MH⁺).

References:

US2009/306089,2009,A1 Location in patent:Page/Page column 33