Ethyl Acetate → 3-cyclopentyl-2-[6-oxo-4-(4-trifluoromethyl-pyrimidin-2-yloxy)-6H-pyridazin-1-yl]-propionic acid

HRID 2381400Notes

Reaction equation

C[O:2][C:3](=[O:29])[CH:4]([N:11]1[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:13]=[N:12]1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Na+].C(OCC)(=O)C>O1CCOCC1>[CH:6]1([CH2:5][CH:4]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[N:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=[CH:21][N:20]=3)[CH:13]=[N:12]2)[C:3]([OH:29])=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 3-cyclopentyl-2-[6-oxo-4-(4-trifluoromethyl-pyrimidin-2-yloxy)-6H-pyridazin-1-yl]-propionic acid methyl ester (0.2 g, 0.48 mmol) in dioxane (2 mL) was treated with a 6N aqueous sodium hydroxide solution (2 mL). The reaction was stirred at 25° C. for 2 d. At this point, ethyl acetate (20 mL) was added and then the aqueous phase was back extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Preparative HPLC afforded 3-cyclopentyl-2-[6-oxo-4-(4-trifluoromethyl-pyrimidin-2-yloxy)-6H-pyridazin-1-yl]-propionic acid as a light oil (20 mg, 10%); 1H NMR (300 MHz, DMSO-d6): δ 9.13 (d, 1H, J=4.8 Hz), 8.24 (d, 1H, J=2.4 Hz), 7.96 (d, 1H, J=4.8 Hz), 7.04 (d, 1H, J=2.4 Hz), 5.38 (dd, 1H, J1=4.5 Hz, J2=10.5 Hz), 2.25˜2.15 (m, 1H), 2.06˜1.97 (m, 1H), 1.71˜1.44 (m, 7H), 1.17˜1.04 (m, 3H). LC-MS: 399.1 [M+1]+, tR=3.04 min.

Workup

extractionthe aqueous phase was back extracted with ethyl acetate
dry with materialThe combined organics were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-52e28379cbab45f1ac01062c95496535
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258134B2

Reaction notes

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