Potassium tert-butoxide → HCID 68426392, compound

Temperature

-78 °C

The crude 2-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-4,5-dichloro-1-(3-methyl-butyl)-1H-pyrrole-3-carboxylic acid ethyl ester (24.1 g, 48.9 mmol) was dissolved in 110 mL of anhydrous THF and cooled to −78° C. in a acetone dry ice bath. A solution of 77.0 mL of 1.0 M potassium tert-butoxide in THF was added slowly to cold solution, and the reaction was stirred at −78° C. for 30 min. and then at room temperature for 10 min. The reaction was quenched with 9.2 mL of acetic acid. The solvent was evaporated off, and the residue was dissolved in methylene chloride (184 mL). Trifluoroacetic acid (184 mL) was added, and the reaction mixture was stirred at ambient temperature for 1 h. The solvent was evaporated off, and the residue was dissolved in 100 mL of methylene chloride. Triethylamine was added until the solution was basic. After air passed the reaction mixture overnight, the solvent was evaporated off. The residue was dissolved in 350 mL of ethyl acetate, and the organic solution was washed with water and saturated sodium chloride solution, dried, filtered, and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-100% ethyl acetate in hexanes to produce 2.23 g of a brown froth. MS: (+) m/z 345.2 (M+1).

1. waitat room temperature for 10 min
2. customThe reaction was quenched with 9.2 mL of acetic acid
3. customThe solvent was evaporated off
4. dissolutionthe residue was dissolved in methylene chloride (184 mL)
5. additionTrifluoroacetic acid (184 mL) was added
6. stirringthe reaction mixture was stirred at ambient temperature for 1 h
7. customThe solvent was evaporated off
8. dissolutionthe residue was dissolved in 100 mL of methylene chloride
9. additionTriethylamine was added until the solution
10. customthe reaction mixture overnight
11. customthe solvent was evaporated off
12. dissolutionThe residue was dissolved in 350 mL of ethyl acetate
13. washthe organic solution was washed with water and saturated sodium chloride solution
14. customdried
15. filtrationfiltered
16. concentrationconcentrated
17. customThe crude product was purified by flash chromatography
18. washeluting from silica gel with a gradient of 0-100% ethyl acetate in hexanes
19. customto produce 2.23 g of a brown froth

ORD record

ord-d7bcbd5664b644a3a5821783bd7f37f0

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07696223B2