Acetic Acid → 2',3'-Dideoxy-4'-thiocytosine

HRID 653990Notes

Reaction equation

HRID 653990 reaction equation
[Si]([O:18][CH2:19][C@H:20]1[S:24][C@@H:23]([N:25]2[CH:32]=[CH:31][C:29]([NH2:30])=[N:28][C:26]2=[O:27])[CH2:22][CH2:21]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=O)C>O1CCCC1.O.C(OCC)C>[C@@H:23]1([N:25]2[CH:32]=[CH:31][C:29]([NH2:30])=[N:28][C:26]2=[O:27])[S:24][C@H:20]([CH2:19][OH:18])[CH2:21][CH2:22]1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 15126108HCID 15126108, compound

Product 1

HCID 4522802',3'-Dideoxy-4'-thiocytosineYield 69%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

The compound 13 (78 mg, 0.17 mmol) was dissolved in 4 mL tetrahydrofuran and then 1 M tetrabutylammonium fluoride in THF (0.2 mL, 0.2 mmol) and acetic acid (11.5 μm, 0.2 mmol) were added, with subsequent stirring at 25° C. overnight. The reaction was diluted with 10 mL water and 10 mL ethyl ether followed by stirring for 5 minutes. The aqueous phase was washed with 20 mL ethyl ether and concentrated in vacuo to 1 mL. The aqueous residue was eluted through a 5-mL Dowex 1×4 (-OH) column with water to remove the tetrabutyl ammonium salts. The crude product (33 mg, 87%) was refractory to recrystallization and was precipitated as an amorphous solid with ethyl acetate and ethyl ether to afford 26.5 mg (69%) of 24; mp. 83°-85° C.; FAB MS 228 (M+H)+ ;1H NMR (DMSO-d6) δ 8.0 (d, 1, H-6), 7.1 (brd, 2, NH2), 6.15 (m, 1, 1'-H), 5.74 (d, 1, H-5), 5.1 (brs, 1, 5'-OH), 4.2 (q, EtOAc), 3.64 (m, 1, 5'-H), 3.5 (m, 2, 4'-H, 5'-H), 2.18 (m, 1, 2'-H), 2.0 (m, 2, 2'-H, 3'-H), 1.99 (s, EtOAc), 1.82 (m, 1, 3'-H), 1.18 (t, EtOAc).

Workup

  1. stirringby stirring for 5 minutes
  2. washThe aqueous phase was washed with 20 mL ethyl ether
  3. concentrationconcentrated in vacuo to 1 mL
  4. washThe aqueous residue was eluted through a 5-mL Dowex 1×4 (-OH) column with water
  5. customto remove the tetrabutyl ammonium salts
  6. customThe crude product (33 mg, 87%) was refractory to recrystallization
  7. customwas precipitated as an amorphous solid with ethyl acetate and ethyl ether

Sources & evidence

ORD record
ord-2377bee7121a4c1ea15386a747e5bc7f
Source dataset
uspto-grants-1992_07
Patent number
US05128458

Reaction notes

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