Potassium Carbonate → 2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine

HRID 1503308Notes

Reaction equation

C(OC([O:8][CH2:9][C@@:10]1([C:24]#[CH:25])[O:14][C@@H:13]([N:15]2[CH:23]=[C:21]([CH3:22])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH:12]=[CH:11]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CO>[C:24]([C@:10]1([CH2:9][OH:8])[O:14][C@@H:13]([N:15]2[CH:23]=[C:21]([CH3:22])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH:12]=[CH:11]1)#[CH:25]

Participants

Conditions

Temperature: 37 °C

Procedure

(2R,5R)-5-t-Butoxycarbonyloxymethyl-5-ethynyl-2-(thymin-1-yl)-2,5-dihydrofuran (5 g) was added to a glass reactor under nitrogen, and methanol (150 g) and potassium carbonate (9.9 g) were added. The mixture was stirred at 37° C. for 4 hours. The reaction mixture was concentrated and dissolved in water. Aqueous sodium hydroxide and toluene were added to the solution under stirring for phase separation, and hydrochloric acid and methyl ethyl ketone were added to the aqueous layer, followed by stirring for further phase separation. The thus-separated organic layer was concentrated, and the residue was purified through recrystallization from ethanol and heptane, to thereby yield 3.2 g of 4′-ethynyl-2′,3′-didehydro-3′-deoxythymidine (yield: 91%, β/α=>99/1). The 1H-NMR data of the compound are the same as those of the compound produced in Example 3.

Workup

concentrationThe reaction mixture was concentrated
dissolutiondissolved in water
additionAqueous sodium hydroxide and toluene were added to the solution
stirringunder stirring for phase separation, and hydrochloric acid and methyl ethyl ketone
additionwere added to the aqueous layer
stirringby stirring for further phase separation
concentrationThe thus-separated organic layer was concentrated
customthe residue was purified through recrystallization from ethanol and heptane

Sources & evidence

ORD record: ord-ec8d2e68a26c4540b5fd3ae691e980bf
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212174B2

Reaction notes

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