Ethoxalyl chloride → ethyl 2-[1-benzyl-5-(3,4-dihydro-2H-1-benzopyran-6-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-oxoacetate

HRID 591078Notes

Reaction equation

C([Mg]Cl)(C)C.[CH2:6]([N:13]1[C:17]([C:18]2[CH:19]=[CH:20][C:21]3[O:26][CH2:25][CH2:24][CH2:23][C:22]=3[CH:27]=2)=[C:16](Br)[C:15]([C:29]([F:32])([F:31])[F:30])=[N:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl[C:34](=[O:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36]>O1CCCC1.O>[CH2:6]([N:13]1[C:17]([C:18]2[CH:19]=[CH:20][C:21]3[O:26][CH2:25][CH2:24][CH2:23][C:22]=3[CH:27]=2)=[C:16]([C:34](=[O:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:15]([C:29]([F:32])([F:31])[F:30])=[N:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

Conditions

Temperature: -20 °C

Procedure

Under nitrogen, isopropyl magnesium chloride 2M in tetrahydrofuran (0.30 mL, 0.59 mmol) was added dropwise to a solution of 1-benzyl-4-bromo-5-(3,4-dihydro-2H-1-benzopyran-6-yl)-3-(trifluoromethyl)-1H-pyrazole (49d) (200 mg, 0.46 mmol) in anhydrous tetrahydrofuran (1.0 mL), previously cooled to −20° C. After 2 hour stirring at the same temperature, ethyl chlorooxoacetate (87 μL, 0.78 mmol) was dropwise added. The mixture was stirred at −20° C. for 60 minutes before being poured in water (2 mL). The mixture was extracted with ethyl acetate (2×3 mL) and the organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (cyclohexane/ethyl acetate 75/25) to provide the desired keto-ester (49e) (80 mg, 0.17 mmol, 38%)

Workup

additionwas dropwise added
extractionThe mixture was extracted with ethyl acetate (2×3 mL)
dry with materialthe organic layer was dried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by preparative TLC (cyclohexane/ethyl acetate 75/25)

Sources & evidence

ORD record: ord-530033280b654a7cb08a0ecc184f8154
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238026B2

Reaction notes

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