Sodium Carbonate → Methyl 5-hydroxy-1-methyl-2-(methylthio)-6-oxo-1,6-dihydropyrimidine-4-carboxylate

In a round-bottomed flask, thiocyanatomethane (17.5 g, 239 mmol) and N-methylhydroxylamine hydrochloride (20 g, 239 mmol) were combined with EtOH (100 ml) to give a light yellow solution. A solution of sodium carbonate (12.7 g, 120 mmol) in water (50 ml) was added slowly over 8 min at RT. The resulting mixture was stirred at RT for 2.5 days and then cooled in an ice bath. Dimethyl but-2-ynedioate (34.0 g, 239 mmol) was added slowly over 10 min and the resulting mixture was stirred for 2 hours, keeping the internal temperature below 22° C. Ice water and EtOAc were added. The organic layer was separated, washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting methyl 5-(2-methoxy-2-oxoethyl)-2-methyl-3-(methylthio)-2,5-dihydro-1,2,4-oxadiazole-5-carboxylate (62.7 g, 239 mmol) was placed in a round-bottomed flask, dissolved in xylene (110 ml), then heated at 140° C. for 48 hours, cooled and then evaporated to dryness to give the crude title product as a brown solid. LCMS: m/z=231 (MH+).

1. customto give a light yellow solution
2. temperaturecooled in an ice bath
3. stirringthe resulting mixture was stirred for 2 hours
4. customthe internal temperature below 22° C
5. customThe organic layer was separated
6. washwashed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. temperatureheated at 140° C. for 48 hours
10. temperaturecooled
11. customevaporated to dryness

ORD record

ord-65a7d724c5524c23894422aa51696a3b

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921388B2