Cyclopentylamine → Methyl 1-cyclopentyl-6-oxo-1,6-dihydropyridine-3-carboxylate

HRID 253097Notes

Reaction equation

HRID 253097 reaction equation
O=[C:2]1[O:7][CH:6]=[C:5]([C:8]([O:10][CH3:11])=[O:9])[CH:4]=[CH:3]1.[CH:12]1([NH2:17])[CH2:16][CH2:15][CH2:14][CH2:13]1>O1CCOCC1>[CH:12]1([N:17]2[C:2](=[O:7])[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:6]2)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

4

Reactant 2

HCID 2906CyclopentylamineHCID 80113Methyl coumalate

Product 1

HCID 66844659Methyl 1-cyclopentyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 6-oxo-6H-pyran-3-carboxylate (Aldrich, 4.00 g, 26.0 mmol) was placed in a 500 mL rbf before 1,4-dioxane (40.0 mL) was added via syringe. After 5 min, cyclopentyl amine (13.0 mL) was added via syringe and the reaction was allowed to stir for 14 h before the volatiles were removed by rotary evaporation. The solid residue was dissolved in diethyl ether (100 mL) and then washed with HCl (10%, 1×100 mL), NaHCO3 (sat, 1×100 mL), brine (sat 100 mL), and dried with magnesium sulfate. The dried solution was filtered and concentrated to provide 4.95 g of crude oil which was purified by a 120 g normal phase Isco column chromatography (50% EtOAc-100% EtOAc in hexanes) to give 2.38 g of methyl 1-cyclopentyl-6-oxo-1,6-dihydropyridine-3-carboxylate. MS m/z: 222 (M+1). This methyl ester was dissolved in THF (30 mL) and water was added (10 mL) before the addition of LiOH monohydrate (1.20 g) and then reaction was placed in a 70° C. oil bath for 2 h. The reaction was cooled and the bulk of the THF was removed by rotary evaporation. The reaction was then poured into a separatory funnel and HCl (10%, 75 mL) was added before extracting with diethyl ether (3×100 mL). The combined organics were washed with brine (sat, 200 mL) and dried with magnesium sulfate. The solution was filtered and concentrated to provide an off white solid (920 mg). MS m/z: 208 (M+1).

Workup

  1. additionwas added via syringe
  2. customwere removed by rotary evaporation
  3. dissolutionThe solid residue was dissolved in diethyl ether (100 mL)
  4. washwashed with HCl (10%, 1×100 mL), NaHCO3 (sat, 1×100 mL), brine (sat 100 mL)
  5. dry with materialdried with magnesium sulfate
  6. filtrationThe dried solution was filtered
  7. concentrationconcentrated
  8. customto provide 4.95 g of crude oil which
  9. customwas purified by a 120 g normal phase Isco column chromatography (50% EtOAc-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-03fab3698ff7472ba25ecfc8873631fb
Source dataset
uspto-grants-2011_01
Patent number
US07872009B2

Reaction notes

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