Hoffer's chlorosugar → 2-Chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purine

HRID 2264881Notes

Reaction equation

HRID 2264881 reaction equation
[Na].[Cl:2][C:3]1[N:11]=[C:10]2[C:6]([NH:7][CH:8]=[N:9]2)=[C:5]([N:12]2[CH:16]=[CH:15][N:14]=[C:13]2[CH2:17][CH2:18][CH3:19])[N:4]=1.[C:20]1([CH3:46])[CH:25]=[CH:24][C:23]([C:26]([O:28][C@@H:29]2[C@@H:33]([CH2:34][O:35][C:36]([C:38]3[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=3)=[O:37])[O:32][C@H:31](Cl)[CH2:30]2)=[O:27])=[CH:22][CH:21]=1>CC#N.C(Cl)Cl>[Cl:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@@H:31]2[O:32][C@H:33]([CH2:34][O:35][C:36]([C:38]3[CH:39]=[CH:40][C:41]([CH3:44])=[CH:42][CH:43]=3)=[O:37])[C@@H:29]([O:28][C:26]([C:23]3[CH:22]=[CH:21][C:20]([CH3:46])=[CH:25][CH:24]=3)=[O:27])[CH2:30]2)=[C:5]([N:12]2[CH:16]=[CH:15][N:14]=[C:13]2[CH2:17][CH2:18][CH3:19])[N:4]=1

Participants

6

Reactant 3

HCID 98571Hoffer's chlorosugarHCID 5360545SodiumHCID 115579952-Chloro-6-(2-propylimidazol-1-yl)purine

Product 1

HCID 160880882-Chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purineYield 95%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

This reaction was repeated on a larger scale with the sodium salt of 2-chloro-6-(2-propylimidazol-1-yl)purine (1.54 g, 5.87 mmol) in dried CH3CN (100 mL) treated with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (3.74 g, 9.62 mmol) in CH2Cl2 (100 mL) by general method 2 for 5 h (reaction complete, TLC). Sampling at different reaction times showed no α-nucleoside by 1H NMR (500 MHz). Volatiles were evaporated, and the residue was dissolved in CH2Cl2. The solution was washed (H2O) and dried (Na2SO4), and volatiles were evaporated in vacuo. The residue was chromatographed (EtOAc/hexanes, 1:1→7:3) to give 2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purine (3.42 g, 95%). Recrystallization from EtOAc gave the β-anomer (2.75 g, 76%).

Workup

  1. custom(reaction complete, TLC)
  2. aliquotSampling at different reaction times
  3. customVolatiles were evaporated
  4. dissolutionthe residue was dissolved in CH2Cl2
  5. washThe solution was washed (H2O)
  6. dry with materialdried (Na2SO4), and volatiles
  7. customwere evaporated in vacuo
  8. customThe residue was chromatographed (EtOAc/hexanes, 1:1→7:3)

Sources & evidence

ORD record
ord-f4847b84b2df4efeaaf10ba134b44290
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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