Ethylamine → Bimatoprost

Temperature

-10 °C

250 mL of methylene chloride were added to 12.3 g of (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-((R)-3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-hept-5-enoic acid (compound (7), MW=402.54; 26.1 mmol; 1 equivalents). The solution is cooled to −10° C. At this temperature 5.1 g of triethylamine (MW=101.19; 50.4 mmol; 1.9 equivalents) and 5.1 g of ethyl chloroformate (MW=108.52; 48.1 mmol; 1.8 equivalents) were added and the mixture was stirred for two hours. A solution of 2.3 g of ethylamine (MW=45.08; 2.0 equivalents) in 10 mL methylenehloride was added. After stirring the reaction mixture for two hours at −10° C., the mixture was warmed to room temperature. The reaction was quenched by addition of 250 mL of water and the pH is adjusted to 2.0 with 1M aqueous hydrochloric acid. After separation of the layers, the organic layer was washed with 250 mL of saturated aqueous sodium bicarbonate, water and brine. After filtration the solution was concentrated under reduced pressure to give 13.1 g of bimatoprost crude (yield: 89%; as determined by NMR). Bimatoprost crude was purified as described below.

1. stirringAfter stirring the reaction mixture for two hours at −10° C.
2. temperaturethe mixture was warmed to room temperature
3. customThe reaction was quenched by addition of 250 mL of water
4. customAfter separation of the layers
5. washthe organic layer was washed with 250 mL of saturated aqueous sodium bicarbonate, water and brine
6. filtrationAfter filtration the solution
7. concentrationwas concentrated under reduced pressure

ORD record

ord-4c41273e92cf475796f6d931c5575b29

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772544B2