Diisopropylcarbodiimide → (S)-2,5-dioxopyrrolidin-1-yl 2-(methoxycarbonylamino)-3-methylbutanoate

Temperature

2.5 °C

To a mixture of (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (19.66 g, 112 mmol) and N-hydroxysuccinimide (13.29 g, 116 mmol) was added ethyl acetate (250 ml), and the mixture was cooled to 0-5° C. Diisopropylcarbodiimide (13.88 g, 110 mmol) was added and the reaction mixture was stirred at 0-5° C. for about 1 hour. The reaction mixture was warmed to room temperature. The solids (diisopropylurea by-product) were filtered and rinsed with ethyl acetate. The filtrate was concentrated in vacuo to an oil. Isopropyl alcohol (200 ml) was added to the oil and the mixture was heated to about 50° C. to obtain a homogeneous solution. Upon cooling, crystalline solids formed. The solids were filtered and washed with isopropyl alcohol (3×20 ml) and dried to give the title compound as a white solid (23.2 g, 77% yield).

1. temperatureThe reaction mixture was warmed to room temperature
2. filtrationThe solids (diisopropylurea by-product) were filtered
3. washrinsed with ethyl acetate
4. concentrationThe filtrate was concentrated in vacuo to an oil
5. additionIsopropyl alcohol (200 ml) was added to the oil
6. temperaturethe mixture was heated to about 50° C.
7. customto obtain a homogeneous solution
8. temperatureUpon cooling
9. customcrystalline solids formed
10. filtrationThe solids were filtered
11. washwashed with isopropyl alcohol (3×20 ml)
12. customdried

ORD record

ord-79d792d05cd04d878dae94a9ae495b2e

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691938B2