Sodium hydride → HCID 66875397, compound

HRID 2381304Notes

Reaction equation

HRID 2381304 reaction equation
[O:1]([C:8]1[CH:13]=[N:12][NH:11][C:10](=[O:14])[CH:9]=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>O1CCCC1>[CH3:17][O:18][C:19](=[O:28])[CH:20]([N:11]1[C:10](=[O:14])[CH:9]=[C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:13]=[N:12]1)[CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×HCID 66875319HCID 66875319, compound

Product 1

HCID 66875397HCID 66875397, compoundYield 66.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-phenoxy-2H-pyridazin-3-one (1.42 g, 7.54 mmol) in tetrahydrofuran (37.7 mL, 0.2M) cooled to 0° C. was treated with a 60% suspension of sodium hydride in mineral oil (362 mg, 9.05 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, 1.95 g, 8.30 mmol). The reaction was then warmed to 50° C., where it stirred for 18 h. After this time, the reaction was partitioned between water (300 mL) and methylene chloride (3×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (Isco 40 g, 20% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(6-oxo-4-phenoxy-6H-pyridazin-1-yl)-propionic acid methyl ester (1.72 g, 66%) as a clear oil; ES+-HRMS m/e calcd for C19H22N2O4 [M+H+] 343.1653, found 343.1652.

Workup

  1. waitat 25° C. for an additional 30 min
  2. temperatureThe reaction was then warmed to 50° C.
  3. stirringwhere it stirred for 18 h
  4. customAfter this time, the reaction was partitioned between water (300 mL) and methylene chloride (3×100 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c691b477de5b487181c1ad0119ca0b38
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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