1-methoxy-5-methylhexane-2,4-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-methoxy-5-methylhexane-2,4-dione (1.08 g, 6.8 mmol) in EtOH (15 mL) was added guanidine hydrochloride (1.3 g, 13.7 mmol). 5 min later, a solution of Na2CO3 (1.45 g, 13.7 mmol) in H2O was added and the resulting mixture was heated to reflux for 20 h. The reaction was cooled to room temperature and the solvent was removed. The residue was dissolved in EtOAc (20 mL) and H2O (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layer was washed with brine, dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (50% EtOAc in hexanes) to provide 4-isopropyl-6-(methoxymethyl)pyrimidin-2-amine (482 mg, 39%). 1H NMR (CDCl3): d 6.43 (s, 1H), 6.11 (s, 2H), 4.16 (s, 2H), 3.26 (s, 3H), 2.56-2.66 (m, 1H), 1.03 (d, J=6.9 Hz, 6H). the resulting mixture was heated to reflux for 20 h the solvent was removed The residue was dissolved in EtOAc (20 mL) The layers were separated the aqueous layer was extracted with EtOAc (2×20 mL) The combined organic layer was washed with brine dried with Na2SO4 concentrated under reduced pressure The residue was purified by column chromatography (50% EtOAc in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry of NaH (1.02 g, 26 mmol, washed with anhydrous hexanes) in ether (10 mL) was added methyl methoxyacetate (2.3 mL, 23 mmol) followed by 3-methyl-2-butanone (2.4 mL, 23 mmol) in ether (5 mL). The resulting mixture was stirred for 15 h and became a clear yellow solution. The reaction was quenched with saturated aqueous NH4Cl. The resulting mixture was extracted with EtOAc (2×20 mL). The combined organic layer was washed with H2O, brine, dried with Na2SO4 and concentrated under reduced pressure to provide 1-methoxy-5-methylhexane-2,4-dione (2.90 g, 80%) as a mixture of keto and enol form. The reaction was quenched with saturated aqueous NH4Cl The resulting mixture was extracted with EtOAc (2×20 mL) The combined organic layer was washed with H2O, brine dried with Na2SO4 concentrated under reduced pressure