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

HRID 2381500Notes

Reaction equation

[C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][NH:2]1.[H-].[Na+].[CH3:14][O:15][C:16](=[O:25])[CH:17](Br)[CH2:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1.O>O1CCCC1>[CH3:14][O:15][C:16](=[O:25])[CH:17]([N:2]1[N:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:1]1=[O:11])[CH2:18][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2H-phthalazin-1-one (1.33 g, 9.1 mmol) in tetrahydrofuran (45.5 mL, 0.2M) cooled to 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (437 mg, 10.9 mmol). The reaction was stirred at 0° C. for 5 min and then at 25° C. for 30 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 2.35 g, 10 mmol). The reaction was then warmed to 50° C. where it stirred overnight. At this time, the reaction was cooled to 25° C., poured into water (100 mL), and extracted with methylene chloride (3×100 mL). The organics were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (ISCO, 80 g, 20-50% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(1-oxo-1H-phthalazin-2-yl)-propionic acid methyl ester (1.78 g, 61%) as a clear oil; ES+-HRMS m/e calcd for C17H20N2O3 [M+H+] 301.1547 found 301.1546.

Workup

waitat 25° C. for 30 min
temperatureThe reaction was then warmed to 50° C. where it
stirringstirred overnight
temperatureAt this time, the reaction was cooled to 25° C.
extractionextracted with methylene chloride (3×100 mL)
dry with materialThe organics were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-60cb4ba1d3e441188b29349b85b65f60
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258134B2

Reaction notes

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