tert-Butanol → tert-Butyl 3-oxocyclobutylcarbamate

A 22 L three neck flask was charged with 3-oxocyclobutanecarboxylic acid (630 g, 5.52 mol, 1.0 equiv), toluene (12 L), and triethylamine (850 mL, 6.07 mol, 1.1 equiv). The acid dissolved in toluene after the addition of triethylamine. The solution was cooled below 10° C. and diphenylphosphoryl azide (DPPA) (1.32 L, 6.07 mol, 1.1 equiv) was added dropwise over 15 minutes under N2. The solution was then warmed up to RT and stirred overnight. The reaction mixture was then transferred to 22 L separatory funnel, washed with aqueous NaHCO3 (2×4 L), water (4 L), brine (2 L), dried over MgSO4 and filtered. The filtrate was then transferred to a 22 L three neck flask and to it was added tert-butanol (1260 mL, 13.2 mol, 2.4 equiv). The resultant reaction mixture was then heated at reflux overnight. Upon completion, the reaction mixture was cooled to RT and concentrated under reduced pressure. Another 70 g batch was combined prior to the column purification. The crude residue thus obtained was then purified using column chromatography eluting with ethyl acetate/hexanes (25:75 to 40:60) to afford 350 g of tert-butyl (3-oxocyclobutyl)carbamate (30% yield).

1. temperatureThe solution was cooled below 10° C.
2. customThe reaction mixture was then transferred to 22 L separatory funnel
3. washwashed with aqueous NaHCO3 (2×4 L), water (4 L), brine (2 L)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customThe resultant reaction mixture
7. temperaturewas then heated
8. temperatureat reflux overnight
9. temperatureUpon completion, the reaction mixture was cooled to RT
10. concentrationconcentrated under reduced pressure
11. customto the column purification
12. customThe crude residue thus obtained
13. customwas then purified
14. washeluting with ethyl acetate/hexanes (25:75 to 40:60)

ORD record

ord-4284347bce7f49bb981a4dceccd4ff28

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952037B2