Ethylamine → Bimatoprost

Temperature

-10 °C

Under an atmosphere of nitrogen 250 mL methylenechloride were added to 12.34 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) and the solution was cooled to −10° C. At this temperature 5.1 g of triethylamine (MW=101.19; 50.4 mmol; 1.9 equivalents) and 5.8 g of pivalic acid chloride (MW=120.58; 48.1 mmol; 1.8 equivalents) were added. The reaction mixture was stirred for two hours. Then a solution of 2.3 g ethylamine (MW=45.08; 2.0 equivalents) in 10 mL of methylene chloride 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 adding 250 mL of water and adjusting the pH to 2.0 with 1M aqueous hydrochloric acid. After separation of the layers, the organic layers was washed with 250 mL of saturated aqueous sodium bicarbonate, water and brine. After filtration the solution was concentrated under reduced pressure to give 18.4 g of bimatoprost crude (yield: 95%; 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
4. additionby adding 250 mL of water
5. customAfter separation of the layers
6. washthe organic layers was washed with 250 mL of saturated aqueous sodium bicarbonate, water and brine
7. filtrationAfter filtration the solution
8. concentrationwas concentrated under reduced pressure

ORD record

ord-5c8a60e5231f4723835723a81036244a

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772544B2