Reaction #1416

Reaction equation

methyl iodide

Cesium carbonate

N2 [(1,1-dimethylethoxy)carbonyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine

water methanol

→

N2 [(1,1-Dimethylethoxy)carbonyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine, methyl ester

Solvents

—

hexanes

ethyl acetate

ethyl acetate

Conditions

Workup

1. 1
   Otherthe residual water removed azeotropically with acetonitrile (3×)
2. 2
   OtherThe resulting oil was dried in vacuo
3. 3
   workup.DISSOLUTIONdissolved in dry dimethyl-formamide
4. 4
   Washwashed successively with water (2×25 ml.), saturated sodium bicarbonate (25 ml.) and brine (25 ml.)
5. 5
   DryingThe organic phase was dried (anhydrous magnesium sulfate)
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated to dryness
8. 8
   Otherdried in vacuo
9. 9
   Otherto give 10.11 g

Procedure

Cesium carbonate (4.28 g., 13.1 moles) was added to a mixture of N2 -[(1,1-dimethylethoxy)carbonyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine (10 g., 26.3 moles) and 20% water-methanol (60 ml.). The solution became homogeneous within 5 minutes so the solvent was stripped and the residual water removed azeotropically with acetonitrile (3×). The resulting oil was dried in vacuo, dissolved in dry dimethyl-formamide and treated with methyl iodide (3.2 ml., 2.0 eq.). The reaction mixture was stirred at room temperature for 1.5 hours under argon, diluted with ethyl acetate (200 ml.) and washed successively with water (2×25 ml.), saturated sodium bicarbonate (25 ml.) and brine (25 ml.). The organic phase was dried (anhydrous magnesium sulfate), filtered, evaporated to dryness and dried in vacuo to give 10.11 g., of product as a light yellow syrup; Rf =0.30 (ethyl acetate:hexanes, 1:2).

Source