Triethylamine → HCID 57636788, compound

Temperature

120 °C

(1S,1aR,7bS)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-carboxylic acid (0.5 g, 2.2 mmol, ˜95% ee) was mixed with toluene (3 ml), triethylamine (0.34 ml, 1.1 eq), DPPA (0.52 ml, 1.1 eq) and bubbled with argon for about 5 min. The reaction mixture was then heated at stirring at 120° C. for 1.5 h under argon. The temperature was then decreased to 50° C. and a mixture of 3 ml of 10% hydrochloric acid in 10 ml dioxane was added. The reaction mixture was stirred for 2 h at 50° C. and then concentrated by rotary evaporation. The residue was mixed with water ant diethyl ether. Water phase was collected and basified with 28% aqueous ammonia to pH 11 and extracted into ether (3×20 ml). Combined organic phases were washed with water and brine and dried over magnesium sulfate. Concentration by rotary evaporation gave 310 mg of crude product as yellow orange oil. The product was purified by column chromatography on silica (30 g, EtOAc/hexane 1:2) to give 220 mg of colorless oil (50% yield).

1. custombubbled with argon for about 5 min
2. temperatureThe reaction mixture was then heated
3. customwas then decreased to 50° C.
4. additiona mixture of 3 ml of 10% hydrochloric acid in 10 ml dioxane
5. additionwas added
6. stirringThe reaction mixture was stirred for 2 h at 50° C.
7. concentrationconcentrated by rotary evaporation
8. additionThe residue was mixed with water ant diethyl ether
9. customWater phase was collected
10. extractionextracted into ether (3×20 ml)
11. washCombined organic phases were washed with water and brine
12. dry with materialdried over magnesium sulfate
13. concentrationConcentration
14. customby rotary evaporation
15. customgave 310 mg of crude product as yellow orange oil
16. customThe product was purified by column chromatography on silica (30 g, EtOAc/hexane 1:2)

ORD record

ord-f728872d98624515a5dd369eef496b21

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07517992B2