Boron Trichloride → (2R,3R)-2-((3,4-Dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl)butane-1,3-diol

To a cold (−77° C., acetone/dry ice bath) solution of 5 (2.0 g, 3.72 mmol) in 100 ml of anhydrous dichloromethane was added (via syringe) 38 ml of 1M BCl3 in dichloromethane over 5 min. The reaction was stirred for 6 hrs until no more changes were observed by HPLC analysis and then quenched by adding a mixture of pyridine (26 ml) and methanol (54 ml) over 5 min. The reaction mixture was allowed to warm up to room temperature and concentrated. The resultant material was re-dissolved in methanol (100 ml) and co-evaporated twice with triethylamine (10 ml) to remove pyridine. The residue was suspended in dichloromethane and filtered to remove some triethylammonium chloride. The solid were washed with dichloromethane and the combined filtrates were concentrated and then chromatographed on silica eluting with 10% methanol in dichloromethane. Concentration of the pure product fractions afforded 0.6 g (70%) of nucleoside 6. 1H NMR (DMSO-d6): δ 11.19 (s, 1H), 7.46 (s, 1H), 4.56 (d, J=4.8 Hz, 1H), 4.50 (t, J=5.1 Hz, 1H), 3.83 (m, 1H), 3.73 (m, 1H), 3.57 (m, 1H), 3.38 (m, 2H), 1.75 (s, 3H), 1.73 (m, 1H). 1.10 (d, J=6.3 Hz, 3H).

1. customquenched
2. additionby adding
3. additiona mixture of pyridine (26 ml) and methanol (54 ml) over 5 min
4. concentrationconcentrated
5. dissolutionThe resultant material was re-dissolved in methanol (100 ml)
6. customto remove pyridine
7. filtrationfiltered
8. customto remove some triethylammonium chloride
9. washThe solid were washed with dichloromethane
10. concentrationthe combined filtrates were concentrated
11. customchromatographed on silica eluting with 10% methanol in dichloromethane

ORD record

ord-9a992305b4d54e6184ef8722cf97c75a

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169256B2