Methanol → HCID 90092468, compound

Under nitrogen atmosphere, to a solution of 4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(thiophen-3-yl)-1H-pyrazole-5-carbaldehyde (4d) (150 mg, 0.46 mmol) in anhydrous dichloromethane (2 mL) at 0° C. were successively added zinc iodide (15 mg, 0.05 mmol) and trimethylsilyl cyanide (69 μL, 0.55 mmol). The reaction mixture was stirred at room temperature for 2 hours. A saturated solution of sodium hydrogenocarbonate (5 mL) was added. Layers were separated and the aqueous layer was extracted with dichloromethane (2×6 mL). The organic layers were dried over sodium sulfate and concentrated in vacuo. The residue, dissolved in anhydrous methanol (3 mL) was added to a solution of acetyl chloride (0.39 mL, 5.55 mmol) in anhydrous methanol (2 mL), previously stirred for 20 minutes at 0° C. under nitrogen atmosphere. The mixture was stirred at room temperature for 24 hours. The solution was concentrated in vacuo and saturated solution of sodium hydrogenocarbonate (5 mL) was added to the residue. The aqueous layer was extracted with ethyl acetate (2×6 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (cyclohexane/ethyl acetate 45/55) to provide methyl 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(thiophen-3-yl)-1H-pyrazol-5-yl]-2-hydroxyacetate (4e) (117 mg, 0.30 mmol, 66%).

1. customat 0° C.
2. customLayers were separated
3. extractionthe aqueous layer was extracted with dichloromethane (2×6 mL)
4. dry with materialThe organic layers were dried over sodium sulfate
5. concentrationconcentrated in vacuo
6. dissolutionThe residue, dissolved in anhydrous methanol (3 mL)
7. stirringpreviously stirred for 20 minutes at 0° C. under nitrogen atmosphere
8. stirringThe mixture was stirred at room temperature for 24 hours
9. concentrationThe solution was concentrated in vacuo and saturated solution of sodium hydrogenocarbonate (5 mL)
10. additionwas added to the residue
11. extractionThe aqueous layer was extracted with ethyl acetate (2×6 mL)
12. dry with materialThe organic layer was dried over sodium sulfate
13. concentrationconcentrated in vacuo
14. customThe residue was purified by preparative TLC (cyclohexane/ethyl acetate 45/55)

ORD record

ord-5989772cc09b49eba3d2e089b6af0fcb

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260395B2