Tetramethyltin → Ethyl 2-amino-6-methylnicotinate

HRID 78176Notes

Reaction equation

HRID 78176 reaction equation
[CH3:1]N1CCCC1=O.[CH2:8]([O:10][C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15](Cl)=[N:14][C:13]=1[NH2:19])[CH3:9].C[Sn](C)(C)C>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.O>[CH2:8]([O:10][C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([CH3:1])=[N:14][C:13]=1[NH2:19])[CH3:9]

Participants

6

Reactant 3

HCID 11661TetramethyltinHCID 13387N-methyl-2-pyrrolidoneHCID 45926148Ethyl 2-amino-6-chloronicotinate

Product 1

HCID 12494686Ethyl 2-amino-6-methylnicotinateYield 48%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

To a N-methylpyrrolidinone (20 mL) solution of 2-amino-6-chloro-nicotinic acid ethyl ester (2.00 g, 7.78 mmol) described in Manufacturing Example 170-1-1 were added tetramethyltin (1.62 mL, 11.7 mmol) and tetrakis(triphenylphosphine)palladium(0) (899 mg, 0.778 mmol), which was stirred under nitrogen atmosphere for 5 hours and 40 minutes at 130° C. Water was added to the reaction mixture at room temperature, which was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered, and the filtrate was concentrated under a reduced pressure. The residue thus obtained was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1), and then further purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (670 mg, 48%).

Workup

  1. extractionwhich was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under a reduced pressure
  6. customThe residue thus obtained
  7. customwas purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1)
  8. customfurther purified by silica gel column chromatography (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-5c8c123564f94553bf85ff1fa6502903
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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