Dimethyl Sulfoxide → methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate
Reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=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(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]1Participants
Conditions
- Temperature
- -78 °C
Procedure
Oxalyl chloride (1.3 mL, 15.5 mmol) was added dropwise to a mixture of dimethyl sulfoxide (1.8 mL, 25.8 mmol) and methylene chloride (4 mL) at −78° C. After addition was complete, the mixture was stirred at −78° C. for 30 min. A solution of methyl 1-(2-hydroxyethyl)-1H-indazole-7-carboxylate (2.8 g, 12.9 mmol) from Step D above in methylene chloride (40 mL) and added dropwise while maintaining the temperature at −78° C. The reaction was then stirred at −78° C. for 1-2 h. The reaction was quenched with N,N-diisopropylethylamine, cooled to 0° C., and sat. NaHCO3 was added. The aqueous phase was extracted several times with methylene chloride and the combined organic layers were dried (Na2SO4), filtered and concentrated to give methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate as a yellow oil (3.8 g, crude): 1H NMR (300 MHz, CDCl3) δ 9.79 (s, 1H), 8.16 (s, 1H), 8.14-8.08 (m, 2H), 7.98 (d, J=7.5 Hz, 1H), 5.61 (s, 2H), 3.99 (s, 3H); MS (ESI+) m/z 219 (M+H).
Workup
- additionAfter addition
- temperaturewhile maintaining the temperature at −78° C
- stirringThe reaction was then stirred at −78° C. for 1-2 h
- customThe reaction was quenched with N,N-diisopropylethylamine
- temperaturecooled to 0° C.
- additionsat. NaHCO3 was added
- extractionThe aqueous phase was extracted several times with methylene chloride
- dry with materialthe combined organic layers were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-76858a79911b45cf8c06ff362ea9e0d6
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08710046B2
Reaction notes
Loading…