Hydrochloric Acid → HCID 23372840, compound

Temperature

0 °C

A solution of the acid from Step 1 (3.11 g, 10.2 mmol) and triethylamine (1.23 g, 10.8 mmol) dissolved in 15 mL of anhydrous toluene, was cooled to 0° C. and treated with diphenylphosphoryl azide (2.98 g, 10.8 mmol). The solution was maintained at 0° C. for twenty minutes and warmed to room temperature for 1 hour. The reaction was poured into water, extracted with ether, dried over magnesium sulfate, and concentrated in vacuo to remove the ether. The remaining toluene solution was diluted with an additional 10 mL of toluene and heated to 90° C. for 1.5 hours. tert-Butyl alcohol (4 mL, 42 mmol) was added to the reaction mixture. After an additional twenty minutes, concentrated hydrochloric acid (4 mL) was cautiously added and the reaction maintained at 90° C. overnight (16 hours). After cooling the solution to room temperature, the mixture was poured into a separatory funnel, diluted with ethyl acetate, and washed with water. The organic layer was dried with anhydrous MgSO4, filtered and concentrated in vacuo to give a yellow solid. The crude solid was crystallized from a mixture of ethyl acetate and hexane to provide the desired ketone (2.19 g, 77%): mp 82°-88.5° C. 1H NMR (CDCl3) 300 MHz 7.91 (q, J=6.0 Hz, 1H), 7.22 (d, J=8.1 Hz, 2H), 7.15 (d, J=8.5 Hz, 2H), 6.82-6.97 (m, 2H), 4.21 (d, J=2.6 Hz, 2H), 2.46 (s, 3H); 19F NMR (CDCl3) -101.74 (m), -104.15 (m). Mass spectrum: M+ =278.

1. temperatureThe solution was maintained at 0° C. for twenty minutes
2. temperaturewarmed to room temperature for 1 hour
3. extractionextracted with ether
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated in vacuo
6. customto remove the ether
7. additionThe remaining toluene solution was diluted with an additional 10 mL of toluene
8. temperatureheated to 90° C. for 1.5 hours
9. waitAfter an additional twenty minutes
10. temperaturethe reaction maintained at 90° C. overnight (16 hours)
11. temperatureAfter cooling the solution to room temperature
12. additionthe mixture was poured into a separatory funnel
13. washwashed with water
14. dry with materialThe organic layer was dried with anhydrous MgSO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customto give a yellow solid
18. customThe crude solid was crystallized from a mixture of ethyl acetate and hexane

ORD record

ord-8dcb47a06182498cb21f59b1ac24cf02

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05668161