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

HRID 321933Notes

Reaction equation

HRID 321933 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-butyldimethylsilyl)-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·2Na(10 ml×2), water and brine
  4. dry with materialdried 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-be705fb2086147d78c70274109f949ce
Source dataset
uspto-grants-2001_04
Patent number
US06211166B1

Reaction notes

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