Red-Al → Methyl 6-amino-5-(hydroxymethyl)-2-methyl-4-(p-tolyl)nicotinate

HRID 1912529Notes

Reaction equation

COCCO[AlH2-]OCCOC.[Na+].[NH2:13][C:14]1[C:19]([C:20](OCC)=[O:21])=[C:18]([C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)[C:17]([C:32]([O:34][CH3:35])=[O:33])=[C:16]([CH3:36])[N:15]=1>O1CCCC1>[NH2:13][C:14]1[C:19]([CH2:20][OH:21])=[C:18]([C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)[C:17]([C:32]([O:34][CH3:35])=[O:33])=[C:16]([CH3:36])[N:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

An ice cold solution of Red-Al (65% in toluene) (3.55 ml, 11.63 mmol) in tetrahydrofuran (THF) (3.3 ml) was treated dropwise with a solution of 3-ethyl 5-methyl 2-amino-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylate (1.91 g, 5.82 mmol) in tetrahydrofuran (THF) (23 ml). After stirring for 1 hour at 0° C., the reaction was quenched with water slowly, then diluted with EtOAc (10 mL) and 20% aq. NaOH (2 mL). The mixture was stirred for 20 min at rt, filtered, extracted with EtOAc, washed with brine, dried with Na2SO4, filtered, and concentrated to afford crude methyl 6-amino-5-(hydroxymethyl)-2-methyl-4-(p-tolyl)nicotinate (1.4679 g, 5.13 mmol, 88% yield) as brown solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.19 (d, J=7.8 Hz, 2 H), 7.03 (d, J=8.0 Hz, 2 H), 5.25 (s, 2 H), 4.42 (s, 2 H), 3.43 (s, 3 H), 2.42 (s, 3 H), 2.38 (s, 3 H); LCMS (m/z) ES+=287 (M+1).

Workup

customthe reaction was quenched with water slowly
additiondiluted with EtOAc (10 mL) and 20% aq. NaOH (2 mL)
stirringThe mixture was stirred for 20 min at rt
filtrationfiltered
extractionextracted with EtOAc
washwashed with brine
dry with materialdried with Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-e12ed311ff0a43c18d67ed24469b7309
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609653B2

Reaction notes

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