Imidazole → 5'-azido-3'-O-t-butyldimethylsilyl-5'-deoxythymidine

HRID 129955Notes

Reaction equation

HRID 129955 reaction equation
[N:1]([CH2:4][C@H:5]1[O:9][C@@H:8]([N:10]2[CH:18]=[C:16]([CH3:17])[C:14](=[O:15])[NH:13][C:11]2=[O:12])[CH2:7][C@@H:6]1[OH:19])=[N+:2]=[N-:3].[Si:20](Cl)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21].N1C=CN=C1>CN(C=O)C>[N:1]([CH2:4][C@H:5]1[O:9][C@@H:8]([N:10]2[CH:18]=[C:16]([CH3:17])[C:14](=[O:15])[NH:13][C:11]2=[O:12])[CH2:7][C@@H:6]1[O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 451456Thymidine, 5'-azido-5'-deoxy-

Product 1

HCID 148429675'-azido-3'-O-t-butyldimethylsilyl-5'-deoxythymidineYield 78.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 25.0 g (93.6 mmol) of 5'-azido-5'-deoxythymidine (which can be prepared as in reference 36), 21.1 g (140 mmol) of t-butyldimethylsilyl chloride, and 12.7 g (187 mmol) imidazole in 190 ml of anhydrous DMF was stirred at RT under nitrogen for 18 hr. The DMF was removed under vacuum. The oil was partitioned between ether (500 ml) and 1N NaOH (2×300 ml). The aqueous layers were cooled with ice, and 650 ml of 1N HCl were added. The product was extracted with EtOAc (2×750 ml), and the organic layer was washed with brine, dried, and evap. After remaining under high vacuum for 24 hr, the oil crystallized to give 27.9 g of 5'-azido-3'-O-t-butyldimethylsilyl-5'-deoxythymidine as a white solid: NMR (300 MHz,d6-DMSO) δ11.34 (br,1H), 7.50 (s,1H), 6.16 (t,1H,J=7 Hz), 4.36 (m,1H), 3.84 (m,1H), 3.55 (m,2H), 2.34 (m,1H), 2.05 (m,1H), 1.79 (s,3H), 0.86 (s,9H), 0.08 (s,6H).

Workup

  1. customThe DMF was removed under vacuum
  2. customThe oil was partitioned between ether (500 ml) and 1N NaOH (2×300 ml)
  3. temperatureThe aqueous layers were cooled with ice, and 650 ml of 1N HCl
  4. additionwere added
  5. extractionThe product was extracted with EtOAc (2×750 ml)
  6. washthe organic layer was washed with brine
  7. customdried
  8. customthe oil crystallized

Sources & evidence

ORD record
ord-059c43f85916450cab7a15aed7a30cdf
Source dataset
uspto-grants-1995_11
Patent number
US05470967

Reaction notes

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