N-methyl-2-pyrrolidone → 2-Amino-6-methoxymethyl-nicotinic acid methyl ester

HRID 1927238Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][C:5]=1[NH2:11].C([Sn](CCCC)(CCCC)[CH2:18][O:19][CH3:20])CCC.CN1C(=O)CCC1.[F-].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:18][O:19][CH3:20])=[N:6][C:5]=1[NH2:11]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 2-amino-6-chloro-nicotinic acid methyl ester (1.4 g) described in Manufacturing Example 11-2, tributyl-methoxymethyl-tin (3.1 g) described in Manufacturing Example 11-3-1, tetrakis(triphenylphosphine)palladium(0) (440 mg), and NMP (20 mL) was stirred for 3.5 hours at 130° C. The reaction solution was allowed to cool, an aqueous potassium fluoride solution and ethyl acetate were added thereto under ice cooling, after which the reaction mixture was filtered through Celite. The organic layer was washed with saturated brine, after which the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the titled compound (0.93 g).

Workup

temperatureto cool
filtrationunder ice cooling, after which the reaction mixture was filtered through Celite
washThe organic layer was washed with saturated brine
customafter which the solvent was evaporated under a reduced pressure
customThe residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record: ord-32c6abe192624bfb9aecc29f23b2ad04
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183264B2

Reaction notes

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