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

HRID 2079943Notes

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 described in Preparation Example A-8 (1.4 g, 7.6 mmol), tributyl-methoxymethyl-stannane (3.1 g, 9.1 mmol) described in Preparation Example A-9, tetrakis(triphenylphosphine)palladium (440 mg, 0.38 mmol) and N-methylpyrrolidinone (20 mL) was stirred at 130° C. for 3.5 hours. The reaction solution was allowed to cool, an aqueous solution of potassium fluoride and ethyl acetate were added thereto on an ice bath, followed by filtering through Celite pad. The organic layer was washed with brine, then, evaporated in vacuo. The residue was purified by silica gel column chromatography (heptane/ethyl acetate=2/1), and the title compound (0.93 g, 4.7 mmol, 63%) was obtained as a light brown oil.

Workup

temperatureto cool
customon an ice bath, followed
filtrationby filtering through Celite pad
washThe organic layer was washed with brine
customevaporated in vacuo
customThe residue was purified by silica gel column chromatography (heptane/ethyl acetate=2/1)

Sources & evidence

ORD record: ord-561013a94b474be0a42bab9c78120420
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932272B2

Reaction notes

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