Water → 3-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester

HRID 2381495Notes

Reaction equation

HRID 2381495 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[N:7][NH:6][C:5](=[O:9])[CH:4]=1.[H-].[Na+].[CH3:12][O:13][C:14](=[O:23])[CH:15](Br)[CH2:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.O>O1CCCC1>[CH3:12][O:13][C:14](=[O:23])[CH:15]([N:6]1[C:5](=[O:9])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[N:7]1)[CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 8206645-Methoxy-2,3-dihydropyridazin-3-oneHCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 668752163-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 5-methoxy-2H-pyridazin-3-one (500 mg, 3.96 mmol) in tetrahydrofuran (19.8 mL, 0.2M) cooled to 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (190 mg, 4.75 mmol). The reaction was stirred at 25° C. for 30 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 1.02 g, 4.36 mmol). The reaction was then warmed to 50° C. where it stirred overnight. After this time, the reaction was cooled to 25° C., was poured into water (100 mL) and was extracted into ethyl acetate (3×75 mL). The organics were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (ISCO 80 g, 40% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester (488 mg, 43%) as a clear oil; ES+-HRMS m/e calcd for C14H20N2O4 [M+H+] 281.1496 found 289.1495. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.92-1.16 (m, 2H), 1.33-1.64 (m, 6H), 1.63-1.78 (m, 1H), 1.89-2.03 (m, 1H), 2.16 (ddd, J=13.9, 10.9, 5.4 Hz, 1H), 3.61 (s, 3H), 3.82 (s, 3H), 5.39 (dd, J=10.7, 4.4 Hz, 1H), 6.32 (d, J=2.7 Hz, 1H), 7.84 (d, J=2.7 Hz, 1H).

Workup

  1. temperatureThe reaction was then warmed to 50° C. where it
  2. stirringstirred overnight
  3. temperatureAfter this time, the reaction was cooled to 25° C.
  4. extractionwas extracted into ethyl acetate (3×75 mL)
  5. dry with materialThe organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-072d45c24ec2465d9826cdf0e286e181
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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