Bromotrimethylsilane → Adefovir

온도

80 °C

9-(2-Hydroxyethyl)adenine (HEA) (20.0 g, 0.112 mol) was suspended in DMF (125 ml) and heated to 80° C. Magnesium isopropoxide (11.2 g, 0.0784 mol), or alternatively magnesium t-butoxide, was added to the mixture followed by diethyl p-toluenesulfonyloxymethylphosphonate (66.0 g, 0.162 mol) over one hour. The mixture was stirred at 80° C. for 7 hours. 30 ml of volatiles were removed via vacuum distillation and the reaction was recharged with 30 ml of fresh DMF. After cooling to room temperature, bromotrimethylsilane (69.6 g, 0.450 mol) was added and the mixture heated to 80° C. for 6 hours. The reaction was concentrated to yield a thick gum. The gum was dissolved into 360 ml water, extracted with 120 ml dichloromethane, adjusted to pH 3.2 with sodium hydroxide, and the resulting slurry stirred at room temperature overnight. The slurry was cooled to 4° C. for one hour. The solids were isolated by filtration, washed with water (2×), and dried in vacuo at 56° C. to yield 20 g (65.4%) of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as a white solid. Mp:>200° C. dec. 1H NMR (D2O) δ 3.49 (t, 2H); 3.94 (t, 2H); 4.39 (t, 2H); 8.13 (s, 1H); 8.22 (s, 1H).

1. custom30 ml of volatiles were removed via vacuum distillation
2. temperatureAfter cooling to room temperature
3. temperaturethe mixture heated to 80° C. for 6 hours
4. concentrationThe reaction was concentrated
5. customto yield a thick gum
6. extractionextracted with 120 ml dichloromethane
7. stirringthe resulting slurry stirred at room temperature overnight
8. temperatureThe slurry was cooled to 4° C. for one hour
9. customThe solids were isolated by filtration
10. washwashed with water (2×)
11. customdried in vacuo at 56° C.

ORD 기록

ord-8cd7c6c8eaed4eedadde19e8a7176674

출처 데이터셋

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07390791B2