Tetrahydrofuran → HCID 59201519, Verbindung

(±)-3-benzyl 7-tert-butyl 3,7-diaza-bicyclo[4.1.0]heptane-3,7-dicarboxylate (62 mg, 0.187 mmol), CuI (8 mg, 0.2 equiv), and a stirring bar were put in a 100-mL flask. The flask was evacuated and backfilled with N2 gas (3×). Dry THF (5 mL) was added and the mixture was cooled to −40° C. (Cyclobutylmethyl)magnesium bromide in THF (620 μL, 3 equiv., ˜0.89 M) was added slowly. After 8 min, the reaction mixture was allowed to warm slowly to rt. After 20 min, the reaction mixture turned black. After stirring a further 2 h the reaction was complete. Satd aq NH4Cl solution (5 mL) was added to quench the reaction. The reaction mixture was partitioned between EtOAc (50 mL) and satd aq NH4Cl solution (20 mL). The aqueous layer was extracted with EtOAc (20 mL). The combined EtOAc layers were washed with water (15 mL), brine (15 mL), and dried over Na2SO4. After concentration, the residue was purified by Gilson to afford (±)-trans-benzyl 3-(tert-butoxycarbonylamino)-4-(cyclobutylmethyl)piperidine-1-carboxylate (14 mg, 19% yield). MS ESI +ve m/z 425 (M+Na).

1. customThe flask was evacuated
2. additionDry THF (5 mL) was added
3. additionwas added slowly
4. waitAfter 20 min
5. customto quench
6. customthe reaction
7. customThe reaction mixture was partitioned between EtOAc (50 mL)
8. extractionThe aqueous layer was extracted with EtOAc (20 mL)
9. washThe combined EtOAc layers were washed with water (15 mL), brine (15 mL)
10. dry with materialdried over Na2SO4
11. concentrationAfter concentration
12. customthe residue was purified by Gilson

ORD-Eintrag

ord-253b0c9fac894f17b17a532e2ffa9bca

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08487108B2