Acetic Acid → 1-O-Acetyl-5-O-t-butyldiphenylsilyl-4-thio-2,3-dideoxyribofuranose

HRID 2260883Notes

Reaction equation

HRID 2260883 reaction equation
[C:1]([S:4][C@H:5]([CH2:12][O:13][Si:14]([C:27]([CH3:30])([CH3:29])[CH3:28])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6]CC(OC)=O)(=[O:3])[CH3:2].CC(C[Al]CC(C)C)C.N1C=CC=CC=1.[C:46](O)(=[O:48])[CH3:47].C([O-])(O)=O.[Na+]>CCCCCC.C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.O>[C:46]([O:3][CH:1]1[S:4][C@H:5]([CH2:12][O:13][Si:14]([C:27]([CH3:30])([CH3:28])[CH3:29])([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6][CH2:2]1)(=[O:48])[CH3:47]

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 1049PyridineHCID 516892Sodium BicarbonateHCID 151260964-(S)-Acetylthio-5-t-butyldiphenylsilyloxypentanoic acid, methyl esterHCID 16682954Dibah

Product 1

HCID 151260981-O-Acetyl-5-O-t-butyldiphenylsilyl-4-thio-2,3-dideoxyribofuranose

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of 9 (1 g, 2.25 mmol) in 14 mL dry hexane and 2 mL toluene was cooled to -78° C. under nitrogen. A 1.5M toluene solution of Dibal-H (3.0 mL, 4.5 mmol) was added over a 2 minute period with stirring continued for an addition 30 minutes. The reaction was quenched with 1.2 mL methanol and allowed to reach 25° C. Then 2.5 mL of saturated NaHCO3 solution was added followed by 1.5 mL ethyl acetate. The mixture was dried with MgSO4. The solids were removed by filtration and washed with ethyl acetate. After removal of solvent in vacuo the residue was redissolved in 20 mL dichloromethane and treated with DMAP (10 mg), pyridine (0.9 mL, 10 mmol) and acetic acid (0.47 mL, 5 mmol) with stirring under nitrogen overnight. The reaction mixture was shaken with 50 mL water, then 50 mL of 1% NaHCO3. After drying (MgSO4), the solvent was removed in vacuo and the residue purified by flash chromatography with 8:1 -hexane/ethyl acetate: yield 0.78 g (83%) of a viscous oil; FAB MS 357 (M-t-butyl)+ ; 1H NMR (CDCl3) δ 7.68 (m, 4, ArH), 7.4 (m, 6, ArH), 6.0 (m, 1, ArH), 3.75 (m, 1, H-5), 3.5 (m, 1, H-4), 3.5 (m, 1, H-5), 2.15 (m, 2, CH2), 2.0 (2s, 3, aromatic acetyls), 1.9 (m, 2, CH2), 1.05 (s, 9, t-butyl).

Workup

  1. additioncontinued for an addition 30 minutes
  2. customThe reaction was quenched with 1.2 mL methanol
  3. customto reach 25° C
  4. additionThen 2.5 mL of saturated NaHCO3 solution was added
  5. dry with materialThe mixture was dried with MgSO4
  6. customThe solids were removed by filtration
  7. washwashed with ethyl acetate
  8. customAfter removal of solvent in vacuo the residue
  9. dissolutionwas redissolved in 20 mL dichloromethane
  10. stirringwith stirring under nitrogen overnight
  11. dry with materialAfter drying (MgSO4)
  12. customthe solvent was removed in vacuo
  13. customthe residue purified by flash chromatography with 8:1 -hexane/ethyl acetate

Sources & evidence

ORD record
ord-05a9b05789394570890399d0620676dd
Source dataset
uspto-grants-1995_12
Patent number
US05478928

Reaction notes

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