Triethyl phosphite → HCID 178520964, compound

HRID 2209755Notes

Reaction equation

HRID 2209755 reaction equation
[C@@H:1]1([N:10]2[C:19]3[N:18]=[CH:17][N:16]=[C:14]([OH:15])[C:13]=3[N:12]=[CH:11]2)[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4](O)[C@H:2]1O.P(OCC)(OCC)OCC.[C@@H]1(N2C3N=CN=C(O)C=3N=C2)O[C@H](CO)C=C1>>[C@@H:1]1([N:10]2[C:19]3[N:18]=[CH:17][N:16]=[C:14]([OH:15])[C:13]=3[N:12]=[CH:11]2)[O:9][C@H:6]([CH2:7][OH:8])[CH2:4][CH2:2]1

Participants

4

Reactant 3

HCID 31215Triethyl phosphiteHCID 1785209639-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-3H-purin-6-oneHCID 178521066(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-hydroxypurin-9-yl)oxolane-3,4-diol2×

Product 1

HCID 178520964HCID 178520964, compoundYield 78%

Procedure

FIG. 3 is an illustration of Scheme 2 according to the present invention for the synthesis of 2',3'-dideoxyinosine In the case of inosine, the dialkyl xanthate (19) was prepared using β-bromopropionitrile instead of methyl iodide in order to avoid N-methylation as observed in uridine when methyl iodide was employed as the alkylating agent (Scheme 5). The 5'-O-t-butyldimethylsilyl inosine 18 was treated with carbon disulfide in the presence of sodium hydroxide and alkylated in situ with bromopropionitrile to obtain 19 in 61% yield after silica gel chromatography. No nitrogen alkylated product was observed. Even if the alkylation at nitrogen did occur, the cyanoethyl group would be eliminated under the basic conditions used. The dialkyl xanthate 19 was found to undergo facile deoxygenation with tributyltin hydride to give 2',3'-unsaturated nucleoside 21 in 85% yield. The unsaturated inosine derivative 21 was also obtained, although in lower yield (39%), from the thionocarbonate 20 by deoxygenation with triethyl phosphite 5'-Desilylation of 21 to 2',3'-didehydro-2',3'-dideoxyinosine (8) followed by catalytic reduction gave the 2',3'-dideoxyinosine (11) in 78% yield.

Workup

  1. customalthough in lower yield (39%)

Sources & evidence

ORD record
ord-f39f5876fe4e4e62ba65b7eb303cfc01
Source dataset
uspto-grants-1995_10
Patent number
US05455339

Reaction notes

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