Reaction #56793

Reaction equation

ethyl 4-bromobutyrate

compound 8b

3-[2(R)-amino-2-(isobutyl)ethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4 (1H,3H)-dione

K2CO3

→

compound 8c

3-[2(R)-{ethoxycarbonylpropyl-amino}-2-(isobutyl)ethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione

Solvents

DMF

Conditions

Workup

1. 1
   Temperaturecooled to room temperature
2. 2
   Otherpartitioned between ethyl acetate and H2O
3. 3
   WashThe organic layer was washed with brine
4. 4
   Dryingdried over Na2SO4
5. 5
   Concentrationconcentrated
6. 6
   OtherThe residue was purified by column chromatography on silica gel with ethyl acetate/hexanes/triethylamine 500/500/5

Procedure

To a solution of compound 8b (25 mg, 0.048 mmol) in DMF (1 mL) was added K2CO3 (21 mg, 0.15 mmol) followed by ethyl 4-bromobutyrate (0.015 mL, 0.1 mmol). The mixture was heated at 95° C. for 16 hours, cooled to room temperature, and partitioned between ethyl acetate and H2O. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel with ethyl acetate/hexanes/triethylamine 500/500/5 to afford compound 8c . MS (CI) m/z 642.2, 644.2 (MH+).

Source