Hydrochloric Acid → HCID 86727121, Verbindung

To a solution of methyl(S)-2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)propanoate (Intermediate 7, 39 g, 146 mmol) in 1,4-dioxane (400 mL) was added 6N HCl (200 mL). The resulting mixture was refluxed for 3 h, then cooled and concentrated under vacuum (water bath temp: 40-45° C.). Water (35 mL) was added to the residue, and the resulting mixture was then stirred for 0.5 h. The precipitate was collected by filtration, washed with cooled water and ethyl acetate to give the (S)-acid (17.3 g, ee: 99%). The filtrate was carefully neutralized with K2HPO4 solution (aq) to pH 4, extracted with (9:1) CH2Cl2:MeOH mixture (2×), dried over MgSO4, filtered, and concentrated. The residue was purified using silica gel chromatography eluting with CH2Cl2:MeOH (9:1) to give additional (S)-acid (3.2 g, ee: 95%).

1. temperatureThe resulting mixture was refluxed for 3 h
2. temperaturecooled
3. concentrationconcentrated under vacuum (water bath temp: 40-45° C.)
4. additionWater (35 mL) was added to the residue
5. filtrationThe precipitate was collected by filtration
6. washwashed with cooled water and ethyl acetate
7. customto give the (S)-acid (17.3 g, ee: 99%)
8. extractionextracted with (9:1) CH2Cl2
9. dry with materialMeOH mixture (2×), dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified
13. washeluting with CH2Cl2:MeOH (9:1)
14. customto give additional (S)-acid (3.2 g, ee: 95%)

ORD-Eintrag

ord-bc5d45d3bc4f4812ac2ec38413669a5a

Quelldatensatz

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09394308B2