Ammonia → N4-(3,5,5-trimethyl-1-hexanoyl)-2'-deoxycytidine

HRID 84065

Reaction equation

HRID 84065 reaction equation
[C@@H:1]1([N:9]2[CH:16]=[CH:15][C:13]([NH2:14])=[N:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.C[Si](Cl)(C)C.[CH3:22][CH:23]([CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:24][C:25](Cl)=[O:26].N>N1C=CC=CC=1>[CH3:22][CH:23]([CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:24][C:25]([NH:14][C:13]1[CH:15]=[CH:16][N:9]([C@@H:1]2[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]2)[C:10](=[O:11])[N:12]=1)=[O:26]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6397ChlorotrimethylsilaneHCID 13711DeoxycytidineHCID 1619293,5,5-Trimethylhexanoyl chloride

Product 1

HCID 86698897N4-(3,5,5-trimethyl-1-hexanoyl)-2'-deoxycytidineYield 127.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Suspending 2′-Deoxycytidine (2.3 g, 10.0 mmol) in dry pyridine, followed by concentration under reduced pressure was repeated 3 times to perform dehydrative azeotropic distillation, the concentrate was suspended again in dry pyridine (60 ml), and trimethylsilyl chloride (6.4 ml, 50 mmol) was added dropwise over 5 min. To the reaction mixture was added 3,5,5-trimethyl-1-hexanoyl chloride (9.5 ml, 50.0 mmol) over 5 min. After completion of the reaction, under ice-cooling, aqueous ammonia (25 ml) was added and the mixture was reacted for 20 min. The reaction mixture was concentrated under reduced pressure. Water (150 ml) was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate (100 ml). The organic layer was concentrated and the obtained oil was purified by silica gel column chromatography to give the title compound (4.7 g).

Workup

  1. concentrationfollowed by concentration under reduced pressure
  2. distillationazeotropic distillation
  3. customAfter completion of the reaction
  4. temperatureunder ice-cooling
  5. customthe mixture was reacted for 20 min
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. additionWater (150 ml) was added to the concentrate
  8. extractionthe mixture was extracted 3 times with ethyl acetate (100 ml)
  9. concentrationThe organic layer was concentrated
  10. customthe obtained oil was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e1342269c6c64ced828ebd7673f082dc
Source dataset
uspto-grants-2014_09
Patent number
US08846885B2

Linked notes

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