Hydrochloric Acid → {1-[2-(Methoxymethyl)-4-nitrophenyl]-2-oxo-1,2-dihydropyridin-3-yl}acetic acid

HRID 2405015Notes

Reaction equation

HRID 2405015 reaction equation
C([O:3][C:4](=[O:30])[CH:5]([C:11]1[C:12](=[O:29])[N:13]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:18]=2[CH2:26][O:27][CH3:28])[CH:14]=[CH:15][CH:16]=1)C(OCC)=O)C.[OH-].[Na+].Cl>O1CCOCC1>[CH3:28][O:27][CH2:26][C:18]1[CH:19]=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:17]=1[N:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH2:5][C:4]([OH:30])=[O:3])[C:12]1=[O:29]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68209743HCID 68209743, compound

Product 1

HCID 68209669{1-[2-(Methoxymethyl)-4-nitrophenyl]-2-oxo-1,2-dihydropyridin-3-yl}acetic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

115 g (maximum 147 mmol) of the crude product of diethyl-{1-[2-(methoxymethyl)-4-nitrophenyl]-2-oxo-1,2-dihydropyridin-3-yl}malonate were introduced as initial charge in 470 ml of dioxane at RT, 940 ml of 2N sodium hydroxide solution were added and the reaction mixture was stirred for 1.5 h at RT. By adding 313 ml of concentrated hydrochloric acid, the pH was adjusted to 1 and the mixture was then stirred for 2 h at 50° C. After cooling to RT, extraction was carried out three times with in each case 1.17 l of ethyl acetate. The combined organic phases, were washed three times with in each case 780 ml of saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and evaporated to dryness on a rotary evaporator. The residue was dissolved in a small amount of dichloromethane and chromatographically purified over 1.96 kg of silica gel (0.04-0.06 mm) with methanol:dichloromethane 5:95 to 1:9. The product fractions were evaporated to dryness on a rotary evaporator. 34.9 g (75% over 2 stages) of the desired product were isolated as oil.

Workup

  1. stirringthe mixture was then stirred for 2 h at 50° C
  2. temperatureAfter cooling to RT
  3. extractionextraction
  4. washThe combined organic phases, were washed three times with in each case 780 ml of saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated to dryness on a rotary evaporator
  8. dissolutionThe residue was dissolved in a small amount of dichloromethane
  9. customchromatographically purified over 1.96 kg of silica gel (0.04-0.06 mm) with methanol:dichloromethane 5:95 to 1:9
  10. customThe product fractions were evaporated to dryness on a rotary evaporator

Sources & evidence

ORD record
ord-ec0e1fc2b0bf4d1f98b3b77fdb3ce619
Source dataset
uspto-grants-2014_08
Patent number
US08802860B2

Reaction notes

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