L-Leucine → L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-

6.56 Grams (0.050 mole) of L-leucine and 10.5 ml. (0.075 mole) of triethylamine were added to 27.5 ml. of water. To the resulting mixture was added a solution of 13.2 g. (0.055 mole) of t-butyl 4,6-dimethyl-pyrimidyl-2-thiolcarbonate in 27.5 ml. of dioxane, and then the mixture was reacted under stirring at room temperature for 10 hours. After completion of the reaction, 75 ml. of water was added to the reaction liquid, and unreacted thiolcarbonate was extracted thrice with 100 ml. of ethyl acetate. Subsequently, the aqueous phase was cooled to 0°C., adjusted to pH 3 by addition of a saturated aqueous citric acid solution, and then extracted once with 75 ml. of ethyl acetate and twice with 40 ml. of ethyl acetate. Thereafter, the ethyl acetate phases were united together, washed once with 50 ml. of an aqueous citric acid solution at pH 1 and twice with 50 ml. of a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate, and then the ethyl acetate was removed by distillation under reduced pressure, whereby a syrupy residue was obtained. This residue was dissolved in 65 ml. of ethanol, and the resulting solution was charged with 50 ml. of water and then cooled to obtain 11.3 g. of crystals of N-t-butyloxycarbonyl-L-leucine monohydrate, yield 97.8 %, m.p. 69° to 74°C. [gradually melting at about 59°C.; Journal of American Chemical Society. 79, 6180 (1957): 67°-72°C⟧

1. additionTo the resulting mixture was added a solution of 13.2 g
2. customAfter completion of the reaction, 75 ml
3. extractionwas extracted thrice with 100 ml
4. temperatureSubsequently, the aqueous phase was cooled to 0°C.
5. additionadjusted to pH 3 by addition of a saturated aqueous citric acid solution
6. extractionextracted once with 75 ml
7. washwashed once with 50 ml
8. dry with materialof a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate
9. customthe ethyl acetate was removed by distillation under reduced pressure, whereby a syrupy residue
10. customwas obtained
11. dissolutionThis residue was dissolved in 65 ml
12. customto obtain 11.3 g
13. custom67°-72°C⟧

ORD record

ord-8cdde905218e454d98cda9e8333ee479

Source dataset

uspto-grants-1976_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US03932375