Hydrochloric Acid → 5-Hydroxy-2-(3-methyl-butyl)-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazine-4-carboxylic acid ethyl ester

HRID 30978Notes

Reaction equation

HRID 30978 reaction equation
C(O[C:4](=[O:26])[C:5](=[N:11][N:12]([C:18](=[O:25])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)C.[O-]CC.[Na+].Cl>CCO>[CH2:23]([O:22][C:20]([C:19]1[C:18](=[O:25])[N:12]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[N:11]=[C:5]([C:6]2[S:7][CH:8]=[CH:9][CH:10]=2)[C:4]=1[OH:26])=[O:21])[CH3:24]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 72394125HCID 72394125, compound

Product 1

HCID 597914415-Hydroxy-2-(3-methyl-butyl)-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esterYield 83.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of [(2-Ethoxycarbonyl-acetyl)-(3-methyl-butyl)-hydrazono]-thiophen-2-yl-acetic acid ethyl ester (12a) (380 mg, 1.0 mmol) in EtOH (6 mL) at room temperature, sodium ethoxide (Aldrich) (21 wt % in ethanol, 0.4 mL, 1.1 mmol) was added, and the resulting mixture was stirred for 30 min. Aqueous HCl (5%, 0.75 mL) was added slowly, and then followed by liquid-liquid extraction with H2O/EtOAc. The combined organic layer was washed with brine, dried over MgSO4, concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel to give the desired product (13a) (280 mg, 83%) as yellow solid. LC-MS (ESI+): m/e=337.30 [M+1]+(exact ms: 336.11); 1H NMR (400 MHz, CDCl3): δ 7.89 (dd, 1H, J=3.6, 1.2 Hz), 7.39 (dd, 1H, J=5.2, 1.2 Hz), 7.10 (dd, 1H, J=5.2, 3.6 Hz), 4.53 (q, 2H, J=7.2 Hz), 4.22 (m, 2H), 1.73 (m, 2H), 1.68 (m, 1H), 1.50 (t, 3H, J=7.2 Hz), 0.99 (d, 6H, J=6.4 Hz).

Workup

  1. extractionfollowed by liquid-liquid extraction with H2O/EtOAc
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-a4c0df31ae8940cabdc18cf7376b4cc7
Source dataset
uspto-grants-2008_09
Patent number
US07425552B2

Reaction notes

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