Imidazole → 1-[3-O-(t-Butyldimethylsilyl)-2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl]thymine

HRID 2274444Notes

Reaction equation

HRID 2274444 reaction equation
C([O:4][C@H:5]1[C:9](=[CH2:10])[O:8][C@H:7]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:6]1)(=O)C.N1C=CN=C1.[Si:25](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]>N.CO>[Si:25]([O:4][C@H:5]1[C:9](=[CH2:10])[O:8][C@H:7]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:6]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 670245471-(3-O-Acetyl-2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)-thymine

Product 1

HCID 670244621-[3-O-(t-Butyldimethylsilyl)-2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl]thymineYield 97.3%

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

Compound 8 (5.2 g, 19.53 mmol) in saturated NH3 in MeOH (150 mL) was kept at room temperature for 9 h. After evaporation, the residue was dissolved in DMF (60 mL). To this were added imidazole (5.32 g, 78.12 mmol) and tert-butyldimethylsilyl chloride (8.83 g, 58.59 mmol) at 0° C. The reaction mixture was stirred at room temperature for 11 h, and then partitioned between EtOAc/H2O (250 mL/50 mL×4). Silica gel column chromatography (hexane/EtOAc=10/1) of the organic layer gave 9 (6.43 g, 97%) as a foam: UV (MeOH) λmax 266 nm (ε11600), λmin 236 nm (ε5700); 1H NMR (CDCl3) δ 0.11 and 0.14 (6H, each as s, SiMe), 0.88 (9H, s, SiBu-t), 1.92 (3H, d, J6,CH3=1.2 Hz, Me), 2.03 (1H, dt, Jgem=10.8 Hz, J1′,2′a=3.2 Hz and J2′a,3′=3.2 Hz, H-2′a), 2.61-2.68 (1H, m, H-2′b), 4.25 (1H, d, Jgem=2.2 Hz, H-5′a), 4.57 (1H, d, Jgem=2.2 Hz, H-5′b), 4.68 (1H, dd, J2′a,3′=3.2 Hz, J2′b,3′=6.8 Hz H-3′), 6.46 (1H, dd, J1′,2′a=3.2 Hz and J1′,2′b=7.2 Hz, H-1′), 7.44 (1H, d, J6,CH3=1.2 Hz, H-6), 9.12 (1H, br, NH); FAB-MS m/z 339(M++H). Anal. Calcd for C16H26N2O4Si: C, 56.78; H, 7.74; N, 8.28. Found: C, 56.61; H, 7.87; N, 8.17.

Workup

  1. customAfter evaporation
  2. dissolutionthe residue was dissolved in DMF (60 mL)
  3. custompartitioned between EtOAc/H2O (250 mL/50 mL×4)

Sources & evidence

ORD record
ord-d551371a200d485fa987cab8a78b2b49
Source dataset
uspto-grants-2015_09
Patent number
US09126971B2

Reaction notes

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