反应 #1543054

反应方程式

trimethylsilylacetylene

triethylamine

trimethylsilylacetylene

triethylamine

2'-Deoxy-5-iodo-5'-O-(4-methoxytrityl)uridine

tetraethyl ammonium fluoride hydrate

→

2'-Deoxy-5-ethynyl-5'-O-(4-methoxytrityl)uridine

溶剂

methanol

acetonitrile

N,N-dimethylformamide

chloroform

chloroform

ethyl acetate

反应条件

后处理

1. 1
   其他the solution was vigorously deoxygenated with nitrogen for 30 min
2. 2
   萃取The ethyl acetate solution was extracted with 3×30 ml aqueous 5% ethylenediamine tetra acetic acid disodium salt
3. 3
   洗涤washed with 1×30 ml water
4. 4
   其他Ethyl acetate was removed on the rotary evaporator
5. 5
   其他to give a black foam
6. 6
   workup.STIRRINGthe solution was magnetically stirred for 1 hr
7. 7
   workup.WAITAfter this period the reaction mixture was loaded directly onto a column (2.5 C 30 cm)
8. 8
   洗涤Under medium air pressure (9-12 psi) the column was first eluted with 1 L of chloroform
9. 9
   洗涤1 L of 1% methanol in chloroform and finally with 1 L of 2.5% methanol in chloroform to elute the product

实验过程

2'-Deoxy-5-iodo-5'-O-(4-methoxytrityl)uridine (1.2 g, 1.8 mmol) was dissolved in 6 ml of anhydrous N,N-dimethylformamide (DMF) and the solution was vigorously deoxygenated with nitrogen for 30 min. To the magnetically stirred solution was added 142 mg (0.20 mmol) bis(triphenylphosphine)palladium(II) chloride, 76 mg (0.40 mmol) copper (I) iodide, 0.53 ml (5.40 mmol) of trimethylsilylacetylene and 0.56 ml (4.0 mmol) of triethylamine (Aldrich Chemical Company, Milwaukee, Wis. 53233). The following day identical portions of bis(triphenylphosphine)palladium(II)chloride, copper (I) iodide, trimethylsilylacetylene and triethylamine were added. The reaction was allowed to stir for an additional 5 hrs before being poured into 100 ml ethyl acetate in a separating funnel. The ethyl acetate solution was extracted with 3×30 ml aqueous 5% ethylenediamine tetra acetic acid disodium salt and washed with 1×30 ml water. Ethyl acetate was removed on the rotary evaporator to give a black foam. This foam was dissolved in 5 ml of acetonitrile and 222 mg (1.5 mmol) of tetraethyl ammonium fluoride hydrate (Aldrich Chemical Company, Milwaukee, Wis. 53233) was added and the solution was magnetically stirred for 1 hr. After this period the reaction mixture was loaded directly onto a column (2.5 C 30 cm) packed with silica gel (100 g, 230-400 mesh) in chloroform. Under medium air pressure (9-12 psi) the column was first eluted with 1 L of chloroform, then 1 L of 1% methanol in chloroform and finally with 1 L of 2.5% methanol in chloroform to elute the product. The appropriate product fractions were combined and solvent was removed on a rotary evaporator to 769 mg (1.5 mmol) of a light brown foam: Rf 0.23 (silica, 95:5 chloroform: methanol) ; IR (1% KBr) acetylenic carbon-carbon stretch 2110 cm-1 ; MS (EI, Cl,) 524 (M). 1H NMR (300 MHz, DMSO - d6) δ 11.69 (s, 1H, NH), 7.94 (s, 1H, H6), 7.41-7.21 (m, 10H, Ar H), 6.90 (d, 2H, Ar H, J=8.9 Hz), 6.11-6.07 (overlapping dd, 1H, H1'), 5.30 (d, 1H, 3' OH, J=4.6 Hz), 4.24 (m, 1H, H4'), 3.74 (s, 3H OCH3), 3.41-3.11 (m, overlapping water peak, H5' & H5"), 2.27-2.18 (m, 2H, H2" & H2').

来源