Acetonitrile → HCID 15476568, compound

HRID 1368932Notes

Reaction equation

HRID 1368932 reaction equation
C(O[CH:5]1[S:25][C@H:24]([CH2:26][O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:6]1[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)C.[NH:35]1[CH:42]=[CH:41][C:39]([NH2:40])=[N:38][C:36]1=[O:37].C(#N)C.C[Si](C)(C)N[Si](C)(C)C.Cl[Si](C)(C)C.C[Si](OS(C(F)(F)[F:69])(=O)=O)(C)C>>[CH2:8]([O:7][C@H:6]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:24]([CH2:26][O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[S:25][CH:5]1[N:35]1[CH:42]=[C:41]([F:69])[C:39]([NH2:40])=[N:38][C:36]1=[O:37])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 6

HCID 6342AcetonitrileHCID 6397ChlorotrimethylsilaneHCID 13838HexamethyldisilazaneHCID 65367Trimethylsilyl triflateHCID 10552662HCID 10552662, compoundHCID 178418229Cytosine

Product 1

HCID 15476568HCID 15476568, compound

Procedure

To a suspension of 1-O-acetyl 2,3,5-tri-O-benzyl-4-thio-D-arabinofuranose (478 mg, 1 mmol) and cytosine (129.0 mg, 1 mmol) in anhydrosis acetonitrile (25 mmol) were added consecutively hexamethyldisilazane (HMDS, 162 mg, 1 mmol) and chlorotrimethylsilane (TMSCl, 434 mg, 4 mmol), and the mixture was stirred at room temperature for 0.5 hours. This solution was cooled to −78° C. Trimethylsilyltrifluoromethane sulfonate (267 mg, 1.2 mmol) was added and the resulting solution was stirred at −78° C. for another 2.5 h, after which time the reaction was essentially complete. The mixture was warmed to room temperature, concentrated to a small volume (5 mL), diluted with methylene chloride (50 mL) and then washed with water (20 mL) followed by saturated sodium bicarbonate and water. The organic layer was dried over MgSO4 and evaporated to dryness. The residue was purified by chromatography over silica gel (50 g. elution with CHCl3/MEOH 98:2) to afford 7 as 2:1α,β mixture(425.2 mg 80.0%) as a colorless syrup TLC (95:5 CHCl3/MEOH) Rf 0.65; MS z/e 553 (M+Li)+.

Workup

  1. temperatureThis solution was cooled to −78° C
  2. stirringthe resulting solution was stirred at −78° C. for another 2.5 h
  3. temperatureThe mixture was warmed to room temperature
  4. concentrationconcentrated to a small volume (5 mL)
  5. additiondiluted with methylene chloride (50 mL)
  6. washwashed with water (20 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. customevaporated to dryness
  9. customThe residue was purified by chromatography over silica gel (50 g. elution with CHCl3/MEOH 98:2)
  10. customto afford 7 as 2:1α,β mixture(425.2 mg 80.0%) as a colorless syrup TLC (95:5 CHCl3/MEOH) Rf 0.65

Sources & evidence

ORD record
ord-e75893756f0746cf9f74a231ada483f8
Source dataset
uspto-grants-2003_06
Patent number
US06576621B1

Reaction notes

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