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0 °C

A flask equipped with an overhead stirrer, thermometer and addition funnel was placed under a nitrogen atmosphere then charged with the acid of Example 1 (20.0 g, 154 mmol), and isopropyl acetate (IPAc; 200 mL) then cooled to 0±5° C. 4-Methylmorpholine (NMM, 154 mL, 17 mL) was charged to the addition funnel then added maintaining the temperature at 0±5° C. Once addition was complete the addition funnel washed with IPAc (10 mL) and then charged with isobutyl chloroformate (IBCF, 137 mmol, 19.5 mL) which was added keeping the temperature at 0±5° C. The reaction mixture was stirred at 0±5° C. for 90 min after which time a solution of cyclopropylamine (154 mmol, 10.7) in IPAc (80 mL) was added keeping the temperature at 0±5° C. Upon completion of addition the reaction was warmed to 25±5° C. and allowed to stir for 18 h. Sodium hydroxide (231 mL, 1.0 N) was added and the biphasic mixture stirred vigorously for 30 min, then the layers were separated. The organic phase was then washed with HCl (231 mL, 1.0 N). The combined organic phases were dried over sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound (19.5 g, 75%) as an orange oil.

1. customA flask equipped with an overhead stirrer
2. additionthermometer and addition funnel
3. additionthen added
4. temperaturemaintaining the temperature at 0±5° C
5. additionOnce addition
6. washwashed with IPAc (10 mL)
7. additionwas added
8. customat 0±5° C
9. additionwas added
10. customat 0±5° C
11. additionUpon completion of addition the reaction
12. temperaturewas warmed to 25±5° C.
13. stirringthe biphasic mixture stirred vigorously for 30 min
14. customthe layers were separated
15. washThe organic phase was then washed with HCl (231 mL, 1.0 N)
16. dry with materialThe combined organic phases were dried over sodium sulfate (Na2SO4)
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure