Phenol → Ureidovaline

Temperature

15 °C

To a solution of phenol (2.18 g, 23.2 mmol) in THF (25 mL) was added 50% NaOH solution (1.86 g, 23.2 mmol) at ambient temperature. After the exotherm subsided, N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.95 g, 23.2 mmol) was added. The solution was cooled to 15° C., and then a solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) dissolved in 25 mL of THF was added slowly. An ice bath was used to maintain the temperature between 15 and 20° C. Following a 5 mL THF rinse, the reaction was allowed to warm to ambient temperature. After three hours, an additional aliquot of 50% NaOH solution (90 mg, 2.3 mmol) was added. After 19 hours, the reaction was quenched by the addition of 100 mL of water and the THF removed under reduced pressure. The remaining aqueous phase was washed with MTBE (3×60 mL), toluene (70 mL) was added, and the pH was adjusted to 3.7 with 4 N HCl. The layers were separated, and the aqueous phase was extracted with two additional aliquots (70 mL) of toluene. The combined toluene extracts were concentrated in vacuo. The resulting oil was crystallized using toluene and heptane to give the title compound (5.1 g, 78%).

1. additionwas added slowly
2. customAn ice bath was used
3. temperatureto maintain the temperature between 15 and 20° C
4. washrinse
5. temperatureto warm to ambient temperature
6. waitAfter 19 hours
7. customthe reaction was quenched by the addition of 100 mL of water
8. customthe THF removed under reduced pressure
9. washThe remaining aqueous phase was washed with MTBE (3×60 mL), toluene (70 mL)
10. additionwas added
11. customThe layers were separated
12. extractionthe aqueous phase was extracted with two additional aliquots (70 mL) of toluene
13. concentrationThe combined toluene extracts were concentrated in vacuo
14. customThe resulting oil was crystallized

ORD record

ord-f67184d72d6e48ecad7d5f7020a4092a

Source dataset

uspto-grants-2000_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06160122