4-Penten-1-OL → 3-Methyl-N-{[(pent-4-en-1-yl)oxy]carbonyl}-L-valine

Temperatur

0 °C

DIPEA (9.85 g, 76.2 mmol) was added dropwise to a 0° C. solution of 4-penten-1-ol (7.22 g, 83.9 mmol) and triphosgene (11.3 g, 38.1 mmol) in 160 mL dioxane. The resulting white suspension was stirred for 5 minutes at 0° C., then allowed to warm to 25° C. over 1 hour. The suspension was cooled to 0° C. with an ice bath and 1 N NaOH (76.2 mL) and L-t-butylglycine (10.0 g, 76.2 mmol) were added. The reaction mixture was warmed to 25° C. and stirred for 18 hours. The dioxane was removed in vacuo and the reaction mixture was basified to pH 12 with 1 N NaOH. The aqueous layer was extracted with DCM (3×150 mL), then acidified to pH˜1 with 6 N HCl. The aqueous layer was extracted with DCM (3×150 mL). The combined organic layers were dried over MgSO4 and concentrated to give the compound as a tan oil (13.7 g, 73.9% yield). LRMS (ESI) m/z 244 [(M+H)+; calcd for C12H22NO4 244].

1. temperatureto warm to 25° C. over 1 hour
2. temperatureThe suspension was cooled to 0° C. with an ice bath
3. temperatureThe reaction mixture was warmed to 25° C.
4. stirringstirred for 18 hours
5. customThe dioxane was removed in vacuo
6. extractionThe aqueous layer was extracted with DCM (3×150 mL)
7. extractionThe aqueous layer was extracted with DCM (3×150 mL)
8. dry with materialThe combined organic layers were dried over MgSO4
9. concentrationconcentrated

ORD-Eintrag

ord-191a5b4917344a498543b9525f4c19c4

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08138164B2