Potassium Fluoride → 2-Amino-6-methoxymethyl-nicotinic acid methyl ester
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.[F-].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN1CCCC1=O>[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
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 130 °C
Procedure
A mixture of 2-amino-6-chloro-nicotinic acid methyl ester (1.4 g, 7.6 mmol) described in Production Example 4-1-2, tributyl methoxymethyl stannane (3.1 g, 9.1 mmol) described in Production Example 4-1-3, 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 allowed to cool on standing followed by the addition of aqueous potassium fluoride solution while cooling with ice and filtering through Celite. After washing the organic layer with sat. NaCl, the organic layer was distilled under a reduced pressure. The residue was purified by silica gel column chromatography (heptane/ethyl acetate=2/1) to obtain the title compound (0.93 g, 4.7 mmol, 63%) as a pale brown oil.
Workup
- temperatureto cool
- temperaturewhile cooling with ice
- filtrationfiltering through Celite
- washAfter washing the organic layer with sat. NaCl
- distillationthe organic layer was distilled under a reduced pressure
- customThe residue was purified by silica gel column chromatography (heptane/ethyl acetate=2/1)
Sources & evidence
- ORD record
- ord-54c4cf46d95943c1a6f8563817e749d2
- Source dataset
- uspto-grants-2010_11
- Patent number
- US07829585B2
Reaction notes
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