Reaction #2814

Reaction equation

sodium hydride

IV

(E)-N-tert-Butyloxycarbonyl-4-(5-pyrimidinyl)-3-butene-1-amine

iodomethane

diisopropylamine

→

compound V

Yield 76.1%

(E)-N-Methyl-N-tert-Butyloxycarbonyl-4-(5-pyrimidinyl)-3-butene-1-amine

Yield 76.1%

Solvents

water

1,2-dimethoxyethane

DMF

water

1,2-dimethoxyethane

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at ambient temperature for 3 days
2. 2
   Temperaturecooled
3. 3
   Extractionextracted with chloroform (7×50 mL)
4. 4
   Otherdried (Na2 SO4)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated by rotary evaporation
7. 7
   OtherThe residue was dried under high vacuum at ambient temperature
8. 8
   Otherto give a red-brown oil
9. 9
   OtherThe oil was chromatographed on silica gel (50 g)
10. 10
    Washeluting with ethyl acetate
11. 11
    Concentrationconcentrated by rotary evaporation
12. 12
    Otherdried under high vacuum at ambient temperature

Procedure

Under a nitrogen atmosphere, sodium hydride (0.78 g, 19.5 mmol, 60% dispersion in oil) was added to a stirring solution of IV (0.50 g, 2.0 mmol), 1,2-dimethoxyethane (20 mL), DMF (25 mL), and a trace of diisopropylamine. The mixture was stirred at ambient temperature for 45 min, and a solution of iodomethane (2.59 g, 18.3 mmol) in 1,2-dimethoxyethane (5 mL) was added. The mixture was stirred at ambient temperature for 3 days, cooled, and water (25 mL) was added dropwise. The mixture was diluted with water (200 mL) and extracted with chloroform (7×50 mL). All chloroform extracts were combined, dried (Na2 SO4), filtered, and concentrated by rotary evaporation. The residue was dried under high vacuum at ambient temperature to give a red-brown oil, The oil was chromatographed on silica gel (50 g), eluting with ethyl acetate. Selected fractions were combined, concentrated by rotary evaporation, and dried under high vacuum at ambient temperature to give compound V as a light yellow oil (0.40 g, 76.1%).

Source