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

HRID 2381506Notes

Reaction equation

HRID 2381506 reaction equation
[O:1]([C:8]1[CH:9]=[CH:10][C:11](=[O:14])[NH:12][N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:17][O:18][C:19](=[O:28])[CH:20](Br)[CH2:21][CH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.O>O1CCCC1>[CH3:17][O:18][C:19](=[O:28])[CH:20]([N:12]1[C:11](=[O:14])[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[N:13]1)[CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 468893056-phenoxypyridazin-3(2H)-oneHCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 668759703-cyclopentyl-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionic acid methyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-phenoxy-2H-pyridazin-3-one (0.78 g, 4.18 mmol) in tetrahydrofuran (21 mL, 0.2M) cooled to 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (0.2 g, 5.0 mmol). The reaction was stirred at 0° C. for 5 min and then at 25° C. for 35 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 1.08 g, 4.59 mmol). The reaction was then warmed to 50° C. where it stirred overnight. After this time, the reaction was cooled to 25° C., poured into water (100 mL), and extracted into methylene chloride (3×100 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, rinsed with methylene chloride and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 80 g, 20-40% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(6-oxo-3-phenoxy-6H-pyridazin-1-yl)-propionic acid methyl ester (1.03 g, 72%) as a light yellow oil. 1H-NMR (300 MHz, DMSO-d6) δ ppm 0.98 (d, 2H), 1.32-1.71 (m, 7H), 1.71-1.84 (m, 1H), 1.84-2.05 (m, 1H), 3.59 (s, 3H), 5.19 (dd, J=10.9, 3.9 Hz, 1H), 7.10-7.18 (m, 3H), 7.22 (t, J=7.5 Hz, 1H), 7.42 (t, J=7.5 Hz, 2H), 7.48 (d, J=9.7 Hz, 1H).

Workup

  1. waitat 25° C. for 35 min
  2. temperatureThe reaction was then warmed to 50° C. where it
  3. stirringstirred overnight
  4. temperatureAfter this time, the reaction was cooled to 25° C.
  5. extractionextracted into methylene chloride (3×100 mL)
  6. washThe combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. washrinsed with methylene chloride
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fcda9791db164c9a828e628269fc59fe
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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