Ethyl Acetate → 6-[3-Chloro-4-(ethoxycarbonylmethoxy)phenyl]-4,5-dihydro-3(2H)-pyridazinone

HRID 11318

Reaction equation

HRID 11318 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:15](=O)[CH2:16][CH2:17][C:18]([OH:20])=O)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].O.[NH2:23][NH2:24].C(OCC)(=O)C>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:15]2[CH2:16][CH2:17][C:18](=[O:20])[NH:23][N:24]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 148782884-[3-Chloro-4-(ethoxycarbonylmethoxy)phenyl]-4-oxobutyric acid

Product 1

HCID 136876706-[3-Chloro-4-(ethoxycarbonylmethoxy)phenyl]-4,5-dihydro-3(2H)-pyridazinoneYield 82%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred suspension of 4-[3-chloro-4-(ethoxycarbonylmethoxy)phenyl]-4-oxobutyric acid (9, 21.5 g, 69.2 mmol) in ethanol (200 mL) at 0° C. was added a solution of hydrazine monohydrate (3.4 mL, 69.2 mmol) in ethanol (20 mL). The reaction mixture was then allowed to warm to ambient temperature and stirred at this temperature for 15 minutes before being heated to reflux and stirred at this temperature for 3 hours. Ethyl acetate (40 mL) was added to the hot solution and the mixture was allowed to cool to ambient temperature. The precipitate which formed was filtered off and washed with water (2×100 mL) and cold ethanol (2×100 mL), then dried with suction, then under high vacuum to give 10 as light yellow powder (17.6 g, 82% yield, 99% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.52 (m, 1H); 7.41 (m, 1H); 6.70 (m, 1H); 4.90 (s, 2H); 4.12 (q, 2H); 2.22 (m, 2H); 1.62 (m, 2H); 1.30 (q, 3H).

Workup

  1. temperaturebefore being heated
  2. temperatureto reflux
  3. stirringstirred at this temperature for 3 hours
  4. temperatureto cool to ambient temperature
  5. customThe precipitate which formed
  6. filtrationwas filtered off
  7. washwashed with water (2×100 mL) and cold ethanol (2×100 mL)
  8. customdried with suction

Sources & evidence

ORD record
ord-e465fd2a4d7d484db6d6c5f3ee938d03
Source dataset
uspto-grants-2006_08
Patent number
US07098211B2

Linked notes

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