Acetic Acid → 5'-O-(tert-Butydimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

HRID 1907090Notes

Reaction equation

HRID 1907090 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[OH:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(=O)C.C(OC(=O)C)(=O)C.[CH3:45][S:46]([CH3:48])=O>>[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:30])([F:31])[F:29])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[O:33][CH2:45][S:46][CH3:48])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 866642615'-O-(tert-butydimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

Product 1

HCID 873394095'-O-(tert-Butydimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridineYield 89%

Procedure

To a solution of (2) (1.84 g, 3.7 mmol) in dry DMSO (7 ml) was added acetic acid (3.2 ml) and acetic anhydride (10.2 ml). The mixture was stirred for 2 days at room temperature, before it was quenched with sat. aq. NaHCO3. EtOAc (50 ml) was added and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with sat. aq. NaHCO3 solution and dried (MgSO4). After removing the solvent under reduced pressure, the product (3) was purified by chromatography on silica (EtOAc: petroleum ether 8:2) yielding a clear sticky oil (1.83 g, 89%). 1H NMR (d6 DMSO): δ 0.00 (s, 6H, CH3), 0.79 (s, 9H, tBu), 1.96-2.06 (m, 1H, H-2′), 1.99 (s, 3H, SCH3), 2.20-2.26 (m, 1H, H-2′), 3.63-3.74 (m, 2H, H-5′), 3.92-3.95 (m, 1H, H-4′), 4.11-4.13 (m, 2H, CH2), 4.28-4.30 (m, 1H, H-3′), 4.59 (br s, 2H, CH2), 5.97 (t, J=6.9 Hz, 1H, H-1′), 7.85 (s, 1H, H-6), 9.95 (t, J=5.3 Hz, 1H, NH), 11.64 (s, 1H, NH). Mass (−ve electrospray) calcd for C22H32F3N3O6SSi 551.17. Found 550.

Workup

  1. customwas quenched with sat. aq. NaHCO3
  2. additionEtOAc (50 ml) was added
  3. extractionthe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with sat. aq. NaHCO3 solution
  5. dry with materialdried (MgSO4)
  6. customAfter removing the solvent under reduced pressure
  7. customthe product (3) was purified by chromatography on silica (EtOAc: petroleum ether 8:2)

Sources & evidence

ORD record
ord-e6b3f8f881534486b77d10ce27188189
Source dataset
uspto-grants-2013_12
Patent number
US08597881B2

Reaction notes

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