2-(1-Ethylpropyl)-6-methoxyisonicotinic acid methyl ester → 2-(1-Ethylpropyl)-6-methoxyisonicotinic acid

HRID 245080Notes

Reaction equation

C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[N:7]=[C:6]([CH:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[CH:5]=1>C(O)C.O.[OH-].[Na+]>[CH2:13]([CH:12]([C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([O:10][CH3:11])[N:7]=1)[C:3]([OH:17])=[O:2])[CH2:15][CH3:16])[CH3:14]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid methyl ester (50 g, 0.211 mol) in ethanol (250 mL), water (50 mL) and 32% aq. NaOH (50 mL) is stirred at 80° C. for 1 h. The mixture is concentrated and the residue is dissolved in water (200 mL) and extracted with TBME. The org. phase is separated and washed once with water (200 mL). The TBME phase is discarded. The combined aq. phases are acidified by adding 25% aq. HCl and then extracted with EA (400+200 mL). The combined org. extracts are concentrated. Water (550 mL) is added to the remaining residue. The mixture is heated to 70° C., cooled to rt and the precipitate that forms is collected and dried to give the title compound (40.2 g) as a white solid; LC-MS: tR=0.95 min, [M+1]+=224.04; 1H NMR (D6-DMSO): δ 0.73 (t, J=7.3 Hz, 6H), 1.59-1.72 (m, 4H), 2.52-2.58 (m, 1H), 3.88 (s, 3H), 7.00 (d, J=1.0 Hz, 1H), 7.20 (d, J=1.0 Hz, 1H).

Workup

concentrationThe mixture is concentrated
dissolutionthe residue is dissolved in water (200 mL)
extractionextracted with TBME
customphase is separated
washwashed once with water (200 mL)
additionby adding 25% aq. HCl
extractionextracted with EA (400+200 mL)
concentrationextracts are concentrated
additionWater (550 mL) is added to the remaining residue
temperaturecooled to rt
customthe precipitate that forms is collected
customdried

Sources & evidence

ORD record: ord-19308e688fc743f4b364ffb219359ebe
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658675B2

Reaction notes

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