Sodium hydride → 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-benzyl)-6H-pyridazin-1-yl]-propionic acid methyl ester

HRID 2381363Notes

Reaction equation

HRID 2381363 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][CH:14]=[CH:13][C:4]=1[CH2:5][C:6]1[CH:11]=[N:10][NH:9][C:8](=[O:12])[CH:7]=1.[H-].[Na+].[CH3:21][O:22][C:23](=[O:32])[CH:24](Br)[CH2:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>O1CCCC1.O.C(Cl)Cl>[CH3:21][O:22][C:23](=[O:32])[CH:24]([N:9]1[C:8](=[O:12])[CH:7]=[C:6]([CH2:5][C:4]2[CH:13]=[CH:14][CH:15]=[CH:16][C:3]=2[C:2]([F:1])([F:17])[F:18])[CH:11]=[N:10]1)[CH2:25][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30]1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×HCID 66875357HCID 66875357, compound

Product 1

HCID 668754003-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-benzyl)-6H-pyridazin-1-yl]-propionic acid methyl esterYield 44.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-(2-trifluoromethyl-benzyl)-2H-pyridazin-3-one (219.6 mg, 0.86 mmol) in tetrahydrofuran (4.32 mL, 0.2M) cooled to 0° C. was treated with a 60% suspension of sodium hydride in mineral oil (41 mg, 1.03 mmol). The reaction stirred at 0° C. for 5 min and then at 25° C. for an additional 30 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 223 mg, 0.95 mmol). The reaction was then warmed to 50° C., where it stirred overnight. After this time, the reaction was diluted with water (150 mL) and methylene chloride (30 mL) and the resulting bilayer was extracted with methylene chloride (3×75 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 25-40% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-benzyl)-6H-pyridazin-1-yl]-propionic acid methyl ester (155.9 mg, 44%) as a yellow oil; ES+-HRMS m/e calcd for C21H23N2O3F3 [M+H+] 409.1734, found 409.1733.

Workup

  1. waitat 25° C. for an additional 30 min
  2. temperatureThe reaction was then warmed to 50° C.
  3. stirringwhere it stirred overnight
  4. extractionthe resulting bilayer was extracted with methylene chloride (3×75 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-80e3f55ce5b541a9a7a7bc227209e2bc
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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