Sodium Hydroxide → n-{[(2,2-Dimethylpent-4-en-1-yl)oxy]carbonyl}-3-methyl-l-valine

Temperature

0 °C

DIPEA (2.48 g, 19.2 mmol) was added dropwise to a 0° C. solution of 2,2-dimethylpent-4-en-1-ol (2.24 g, 19.6 mmol) and triphosgene (2.56 g, 8.64 mmol) in 60 mL dioxane. The resulting white suspension was stirred for 5 min at 0° C., then allowed to warm to 25° C. over 1 h. The suspension was cooled to 0° C. with an ice bath, followed by addition of 1 N NaOH (19.2 mL) and L-tert-butylglycine (2.52 g, 19.2 mmol). The reaction mixture was warmed to 25° C. and stirred for 72 h. 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 dichloromethane (3×150 mL), then acidified to pH˜1 with 6 N HCl. The aqueous layer was extracted with dichloromethane (3×150 mL). The combined organic layers were dried over MgSO4 and concentrated to give N-{[(2,2-dimethylpent-4-enyl)oxy]carbonyl}-3-methyl-L-valine as a white powder (4.26 g, 827% yield). LRMS (ESI) m/z 272 [(M+H)+; calcd for C14H26NO4:

1. temperatureto warm to 25° C. over 1 h
2. temperatureThe suspension was cooled to 0° C. with an ice bath
3. temperatureThe reaction mixture was warmed to 25° C.
4. stirringstirred for 72 h
5. customThe dioxane was removed in vacuo
6. extractionThe aqueous layer was extracted with dichloromethane (3×150 mL)
7. extractionThe aqueous layer was extracted with dichloromethane (3×150 mL)
8. dry with materialThe combined organic layers were dried over MgSO4
9. concentrationconcentrated

ORD record

ord-1b7d6b9bd4234832afd2df4612771f73

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470664B2