Dimethylformamide → Boc-Ala-Ala-OMe

Temperature

25 °C

To a cold (−15° C.) solution of Boc-Ala-OH (1.034 g, 5.47 mmol) and NMM (901 μl, 8.20 mmol) in THF (15 mL) was added ECF (538 μl, 5.63 mmol) under N2 atmosphere and vigorously stirred. After 2 min of stirring, a solution of methyl alaninate hydrochloride (840 mg, 6.01 mmol) in a mixture of solvents THF:DMF (4 mL:3 mL) was added to the reaction mixture followed by NMM (1.5 mL, 13.67 mmol) and stirred. After 10 min the mixture was warmed to 25° C. and stirred for further 8 h. THF was removed under reduced pressure and the resulting viscous solution was diluted with water (10 mL) and thoroughly extracted with ethyl acetate. The combined organic extracts were washed with saturated citric acid (10 mL), saturated NaHCO3 (10 mL) and dried over by Na2SO4 and concentrated under reduced pressure to give a residue, which was purified by silica gel flash column chromatograph (EtOAc:Hexane—3:17) to give the desired product as a solid (m.p. 107-108° C.) in good yields (1.48 g, 98.6%). (TLC:EtOAc:Hexanes 7:3—Rf—0.55).

1. stirringAfter 2 min of stirring
2. stirringstirred
3. stirringstirred for further 8 h
4. customTHF was removed under reduced pressure
5. additionthe resulting viscous solution was diluted with water (10 mL)
6. extractionthoroughly extracted with ethyl acetate
7. washThe combined organic extracts were washed with saturated citric acid (10 mL), saturated NaHCO3 (10 mL)
8. dry with materialdried over by Na2SO4
9. concentrationconcentrated under reduced pressure
10. customto give a residue, which
11. customwas purified by silica gel flash column chromatograph (EtOAc:Hexane—3:17)

ORD record

ord-3e5445079f594651824969f315739ce4

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563686B2