Ammonia → HCID 10885302, compound

HRID 1953067Notes

Reaction equation

HRID 1953067 reaction equation
[CH3:1][N:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:3].N1C=CC=CC=1.[Si:16]([O:23][C@@H:24]1[C@H:28]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@@H:27]([CH3:37])[O:26][C@H]1N1C=C(C#C)C(=O)NC1=O)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[NH3:48].[OH2:49]>C(#N)C.C(OCC)(=O)C>[Si:16]([O:23][C@@H:24]1[C@H:28]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@@H:27]([CH3:37])[O:26][C@H:1]1[N:2]1[CH:3]=[C:7]([C:8]#[CH:9])[C:6]([NH2:48])=[N:5][C:4]1=[O:49])([C:19]([CH3:21])([CH3:22])[CH3:20])([CH3:18])[CH3:17]

Participants

8

Reactant 5

HCID 222Ammonia2×HCID 962WaterHCID 1049PyridineHCID 218852-DimethylaminopyridineHCID 15382730HCID 15382730, compound

Product 1

HCID 10885302HCID 10885302, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of dimethylaminopyridine (19.0 g, 155.5 mmol) in acetonitrile (120 ml) and pyridine (12.6 ml, 155.5 mmol) phosphoryl chloride (14.4 g, 93.8 mM) was added dropwise in an ice bath under Ar atmosphere. After stirring the mixture for 1 hour at room temperature, a solution of 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-ethynyluridine (14.9 g, 31.1 mmol) in acetonitrile (80 ml) was added at 5° C. with cooling in an ice bath. The mixture was stirred at room temperature for 2 hours. Then, 25% aq. ammonia solution (10 ml) was added in one portion to the reaction mixture while keeping the temperature below 10° C. A second portion of 25% aq. ammonia solution (65 ml) was added to the reaction mixture while keeping the temperature below 10° C. The mixture was stirred at room temperature for 45 minutes. Then the reaction mixture was diluted with water (200 ml) at room temperature and extracted three times with ethyl acetate. The combined organic layers were washed successively with aq. 1N-hydrochloric acid solution, aq. saturated sodium bicarbonate and brine. The organic layer was dried over MgSO4, filtered and evaporated under reduced pressure. Purification of the residue by silica gel chromatography (using n-hexane:ethyl acetate=2:1 as an eluent) gave 2',3'-bis-O-(tert-butyidimethylsilyl)-5'-deoxy-5-ethynylcytidine (14.8 g, 99% yield).

Workup

  1. temperaturewith cooling in an ice bath
  2. stirringThe mixture was stirred at room temperature for 2 hours
  3. customthe temperature below 10° C
  4. customthe temperature below 10° C
  5. stirringThe mixture was stirred at room temperature for 45 minutes
  6. extractionextracted three times with ethyl acetate
  7. washThe combined organic layers were washed successively with aq. 1N-hydrochloric acid solution, aq. saturated sodium bicarbonate and brine
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customPurification of the residue by silica gel chromatography (

Sources & evidence

ORD record
ord-8ecef4a4944d43f098839718b6d1942d
Source dataset
uspto-grants-2000_09
Patent number
US06114520

Reaction notes

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