Pyridine → HCID 136461648, compound

HRID 1168583Notes

Reaction equation

HRID 1168583 reaction equation
[Si:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[C:35]3[N:34]=[C:32]([NH2:33])[NH:31][C:29](=[O:30])[C:28]=3[N:27]=[CH:26]2)[C@H:22]([O:36][CH2:37][CH2:38][OH:39])[C@@H:21]1[OH:40])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.C[Si](C)(C)Cl.[C:52](Cl)(=[O:56])[CH:53]([CH3:55])[CH3:54]>CCOC(C)=O.O>[Si:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[C:35]3[N:34]=[C:32]([NH:33][C:52](=[O:56])[CH:53]([CH3:55])[CH3:54])[NH:31][C:29](=[O:30])[C:28]=3[N:27]=[CH:26]2)[C@H:22]([O:36][CH2:37][CH2:38][OH:39])[C@@H:21]1[OH:40])([C:14]([CH3:15])([CH3:17])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6397ChlorotrimethylsilaneHCID 62325Isobutyryl chlorideHCID 136461618HCID 136461618, compound

Product 1

HCID 136461648HCID 136461648, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Dried 5′-O-t-butyldiphenylsilyl-2′-O-(hydroxyethyl)-guanosine (55.9 g, <69 mmol) as a crude product was dissolved in anhydrous pyridine (494 mL, 6.11 mol) with cooling to 5° C. and trimethylchlorosilane (62.7 mL, 494 mmol) was added slowly to give a suspension. The reaction mixture was allowed to slowly warm to ambient temperature, and after 1 hour was again cooled to 5° C. Isobutyryl chloride (51.8 mL, 494 mmol) was added and the reaction mixture was allowed to warm to ambient temperature. After 2 hours the reaction mixture was cooled to 5° C. and cold water (100 mL) was slowly added. After stirring for 12 hours, the solvent was evaporated in vacuo at 40° C. to give an oil which was dissolved in EtOAc (2000 mL) and water (200 mL). The mixture was shaken, the organic was separated, washed twice with water (2×200 mL), then with brine (200 mL), and dried with MgSO4. The solvent was evaporated in vacuo to a volume of about 500 mL after which there was a flocculent white solid which was filtered, washed with cold EtOAc (3×5 mL), and dried in vacuo (0.5 torr) at 45° C. with P2O5 for 28 hours to afford the title compound as a white solid (26.74 g, 60%).

Workup

  1. customto give a suspension
  2. temperatureto slowly warm to ambient temperature
  3. temperatureafter 1 hour was again cooled to 5° C
  4. temperatureto warm to ambient temperature
  5. temperatureAfter 2 hours the reaction mixture was cooled to 5° C.
  6. customthe solvent was evaporated in vacuo at 40° C.
  7. customto give an oil which
  8. stirringThe mixture was shaken
  9. customthe organic was separated
  10. washwashed twice with water (2×200 mL)
  11. dry with materialwith brine (200 mL), and dried with MgSO4
  12. customThe solvent was evaporated in vacuo to a volume of about 500 mL after which there
  13. filtrationwas filtered
  14. washwashed with cold EtOAc (3×5 mL)
  15. dry with materialdried in vacuo (0.5 torr) at 45° C. with P2O5 for 28 hours

Sources & evidence

ORD record
ord-4204768a9a2a49568a5b6323b08762cb
Source dataset
uspto-grants-2003_09
Patent number
US06624294B2

Reaction notes

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