Trimethylsilylacetylene → 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-[(trimethylsilyl)ethynyl]-N4-(n-pentyloxycarbonyl)-cytidine

HRID 1953069Notes

Reaction equation

HRID 1953069 reaction equation
[Si:1]([O:8][C@@H:9]1[C@H:13]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C@@H:12]([CH3:22])[O:11][C@H:10]1[N:23]1[CH:38]=[C:37](I)[C:27]([NH:28][C:29]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:30])=[N:26][C:24]1=[O:25])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:40][Si:41]([C:44]#[CH:45])([CH3:43])[CH3:42]>C(Cl)Cl.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Si:1]([O:8][C@@H:9]1[C@H:13]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C@@H:12]([CH3:22])[O:11][C@H:10]1[N:23]1[CH:38]=[C:37]([C:45]#[C:44][Si:41]([CH3:43])([CH3:42])[CH3:40])[C:27]([NH:28][C:29]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:30])=[N:26][C:24]1=[O:25])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 539224752',3'-Bis-o-(tert-butyldimethylsilyl)-5'-deoxy-5-iodo-n4-(n-pentyloxycarbonyl)cytidine

Product 1

HCID 688007502',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-[(trimethylsilyl)ethynyl]-N4-(n-pentyloxycarbonyl)-cytidineYield 26%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-iodo-N4 -(n-pentyloxycarbonyl)cytidine (130 mg, 0.18 mmol) in CH2Cl2 (2 ml) and Et3N(2 ml) Cul (10.7 mg, 0.1056 mmol), Pd(PPh3)2Cl2 (2.6 mg, 0.0036 mmol), and trimethylsilyl-acetylene (58.6 μl, 0.40 mmol) were added and stirred for 2 hours at room temperature under Ar in the dark. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in EtOAc(25 ml×3), washed with 2% aq. EDTA.2Na(10 ml×2), water and brine, dried over Na2SO4 and filtered. The filtrate was evaporated under reduced pressure. The crude product was purified by flash chromatography on SiO2 (eluent: 10% EtOAc/n-hexane) to give 2',3'-bis-O-(tert-butyidimethylsilyl)-5'-deoxy-5-[(trimethylsilyl)ethynyl]-N4 -(n-pentyloxycarbonyl)-cytidine as a colorless amorphous solid. (30.2 mg, 26% yield)

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in EtOAc(25 ml×3)
  3. washwashed with 2% aq. EDTA
  4. dry with material2Na(10 ml×2), water and brine, dried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography on SiO2 (eluent: 10% EtOAc/n-hexane)

Sources & evidence

ORD record
ord-65c9315d1acc4516b1defe96ba060532
Source dataset
uspto-grants-2000_09
Patent number
US06114520

Reaction notes

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