Pyridine → HCID 66783332, compound

HRID 1096767Notes

Reaction equation

HRID 1096767 reaction equation
C([O:5][C@@H:6]1[C@@H:10]([CH2:11][O:12][C:13](=[O:32])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([O:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)=[O:21])[O:9][C@@:8]([SiH](C)C)([N:33]2[CH:41]=[C:39]([CH3:40])[C:37](=[O:38])[NH:36][C:34]2=[O:35])[CH2:7]1)(C)(C)C.F.N1C=CC=CC=1>ClCCl>[N+:29]([C:26]1[CH:27]=[CH:28][C:23]([O:22][C:20]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[C:13]([O:12][CH2:11][C@H:10]2[O:9][C@@H:8]([N:33]3[CH:41]=[C:39]([CH3:40])[C:37](=[O:38])[NH:36][C:34]3=[O:35])[CH2:7][C@@H:6]2[OH:5])=[O:32])=[O:21])=[CH:24][CH:25]=1)([O-:31])=[O:30]

Participants

5

Reactant 3

HCID 1049PyridineHCID 14917Hydrofluoric AcidHCID 131729529HCID 131729529, compound

Product 1

HCID 66783332HCID 66783332, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

O3′-tert.-butyldimethylsilyl-O5′-(2-(4-nitrophenoxycarbonyl)benzoyl)thymidine, PSNp-dT-Si (6f) (24.4 g, 39 mmol) was dissolved in dichloromethane (300 ml). Hydrogen fluoride in pyridine (65% HF, 12.6 ml, 450 mmol) was added and the mixture was stirred at ambient temperature for 5 hours. The reaction was quenched by the addition of solid calcium carbonate (25.9 g) and stirred for 1 hour. After removal of the solid material by filtration the organic phase was extracted with 5% sodium hydrogencarbonate solution (2 times 500 ml) and water (2 times 500 ml). The organic phase was dried over sodium sulfate and concentrated to a foam by evaporation. The foam was dissolved in dichloromethane (120 ml) and added dropwise to a mixture of hexanes and diethylether (8:2, v/v, 1500 ml). The precipitate was filtered off and washed with a small volume of hexanes. Further purification by column chromatography on silica gel (ethyl acetate/hexanes, gradient elution) afforded the product in 99.8% purity by RP-HPLC (18.4 g, 92%). ESI-MS (pos. mode) m/z 512 [M+H]+.

Workup

  1. customThe reaction was quenched by the addition of solid calcium carbonate (25.9 g)
  2. stirringstirred for 1 hour
  3. customAfter removal of the solid material
  4. filtrationby filtration the organic phase
  5. extractionwas extracted with 5% sodium hydrogencarbonate solution (2 times 500 ml) and water (2 times 500 ml)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. concentrationconcentrated to a foam by evaporation
  8. dissolutionThe foam was dissolved in dichloromethane (120 ml)
  9. additionadded dropwise to a mixture of hexanes and diethylether (8:2, v/v, 1500 ml)
  10. filtrationThe precipitate was filtered off
  11. washwashed with a small volume of hexanes
  12. customFurther purification by column chromatography on silica gel (ethyl acetate/hexanes, gradient elution)
  13. customafforded the product in 99.8% purity by RP-HPLC (18.4 g, 92%)

Sources & evidence

ORD record
ord-04090e7eff804a8cab4f0f4b5937a988
Source dataset
uspto-grants-2012_03
Patent number
US08138330B2

Reaction notes

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