Dimethyl Sulfoxide → methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate

HRID 2168495Notes

Reaction equation

CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[C:23]([O:25][CH3:26])=[O:24])[CH:16]=[N:15]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[O:11]=[CH:12][CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[C:23]([O:25][CH3:26])=[O:24])[CH:16]=[N:15]1

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of DMSO (0.4 mL, 5.2 mmol) and methylene chloride (2 mL) at −78° C. was added oxalyl chloride (0.3 mL, 3.1 mmol) dropwise. After 20 min, a solution of methyl 1-(2-hydroxyethyl)-1H-indazole-7-carboxylate (0.6 g, 2.6 mmol) from Step D above in methylene chloride (17 mL) was added and the mixture was stirred at −78° C. for 1.5 h. After N,N-diisopropylethylamine was added, the reaction was cooled to 0° C. and quenched with saturated aqueous ammonium chloride. The aqueous layer was extracted with methylene chloride and the organic extracts were dried (Na2SO4), filtered, concentrated under reduced pressure and purified by preparatory thin layer chromatography (30% ethyl acetate in hexanes) to give methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate (0.3 g, 53%): 1H NMR (500 MHz, CDCl3) δ 9.79 (s, 1H), 8.16 (s, 1H), 8.10-8.09 (m, 1H), 7.99-7.97 (m, 1H), 7.25-7.21 (m, 1H), 5.61 (s, 2H), 3.92 (s, 3H).

Workup

temperaturethe reaction was cooled to 0° C.
customquenched with saturated aqueous ammonium chloride
extractionThe aqueous layer was extracted with methylene chloride
dry with materialthe organic extracts were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
custompurified by preparatory thin layer chromatography (30% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-5236beb998884c6799cd03a85c41eee7
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045501B2

Reaction notes

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