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

HRID 77847Notes

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.CN1CCCC1=O.[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, 7.6 mmol) described in Manufacturing Example 26-1-2, tributyl-methoxymethyl-stannane (3.1 g, 9.1 mmol) described in Manufacturing Example 26-1-3, tetrakis(triphenylphosphine)palladium (440 mg, 0.38 mmol) and N-methylpyrrolidinone (20 mL) was stirred for 3.5 hours at 130° C. The reaction mixture was cooled to room temperature, and aqueous potassium fluoride solution and ethyl acetate were added to the reaction mixture, which was then filtered through a Celite pad. The organic layer was separated and washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:2) to obtain the title compound (0.93 g, 63%).

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationwas then filtered through a Celite pad
customThe organic layer was separated
washwashed with saturated aqueous sodium chloride
customthe solvent was evaporated under a reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:2)

Sources & evidence

ORD record: ord-d37b800ab9ed4299942246771bd8b178
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841327B2

Reaction notes

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