Triethylamine → 2-(1-Azidoethyl)-5-fluoropyrimidine

HRID 415419Notes

Reaction equation

HRID 415419 reaction equation
FC1C(NC2C=C(C)NN=2)=NC([NH:8][C@H:9]([C:11]2[N:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])=NC=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:37]=[N+:38]=[N-].[Na+]>C(Cl)Cl>[N:8]([CH:9]([C:11]1[N:12]=[CH:13][C:14]([F:17])=[CH:15][N:16]=1)[CH3:10])=[N+:37]=[N-:38]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 16659836HCID 16659836, compound

Product 1

HCID 509937232-(1-Azidoethyl)-5-fluoropyrimidineYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round-bottom flask containing 1-(5-fluoropyrimidin-2-yl)ethanol (Method 4, 0.79 g, 5.55 mmol) was charged with triethylamine (0.67 g, 6.66 mmol) and anhydrous DCM (10 ml). The solution was cooled to 0° C., and methanesulfonyl chloride (0.70 g, 4.1 mmol) was added dropwise. The resulting mixture was allowed to stir at room temperature for 2 hours, at which point the volatile components were removed using a rotary evaporator. The residue was dissolved in DMF (15 ml) and treated with sodium azide (0.72 g, 11.1 mmol). The resulting mixture was stirred at room temperature for 60 hours. It was then partitioned between EtOAc and brine. The organic layer was obtained, dried (Na2SO4), and evaporated to dryness. The crude material was purified by silica gel chromatography (by ISCO Combiflash with gradient EtOAc and hexanes) to afford the title compound as a colourless oil (0.60 g, 65% yield over two steps). GC-MS, 167 (M), 138 (M-N2), 125 (M-N3); 1H NMR (CDCl3) δ 8.60 (s, 2H), 4.60 (m, 1H), 1.65 (d, 3H).

Workup

  1. customwere removed
  2. customa rotary evaporator
  3. dissolutionThe residue was dissolved in DMF (15 ml)
  4. stirringThe resulting mixture was stirred at room temperature for 60 hours
  5. customIt was then partitioned between EtOAc and brine
  6. customThe organic layer was obtained
  7. dry with materialdried (Na2SO4)
  8. customevaporated to dryness
  9. customThe crude material was purified by silica gel chromatography (by ISCO Combiflash with gradient EtOAc and hexanes)

Sources & evidence

ORD record
ord-7807f82455674a199f1dd41d28963e4b
Source dataset
uspto-grants-2012_01
Patent number
US08088784B2

Reaction notes

Loading…