Water → Benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate

3-Chlorobenzoperoxoic acid (16.79 g, 97 mmol) was added portionwise under an atmosphere of nitrogen to a stirred solution of benzyl 5,6-dihydropyridine-1(2H)-carboxylate (15.1 g, 69.5 mmol) (available, for example, from Fluorochem) in anhydrous dichloromethane (DCM) (100 mL) cooled using an ice bath. The resulting mixture was allowed to reach rt and stirred for 18 h. Water (100 mL) was added to the reaction mixture and the layers were partitioned. The organic layer was added dropwise to a stirred 5% aqueous solution of NaS2O5 (200 mL). At the end of the addition, the mixture was stirred for a further 1 h, then the layers were separated and the aqueous layer was back extracted with DCM (50 mL×2). The organics were combined and washed with 5% aqueous K2CO3 solution (100 mL×3), followed by brine (100 mL). At this stage peroxide test showed there was still 25 mg/mL peroxide in the organic layer. The organics were therefore added to a stirred solution of 5% NaS2O5(aq) (200 mL) and the resultant biphasic mixture stirred for 1 h. Peroxide test now showed <0.5 mg/mL peroxide. The layers were separated and aqueous layer washed with further DCM (2×50 mL). The combined organics were then dried (Na2SO4). and concentrated in vacuo to afford the crude product as a pale-gold oil. The crude product was purified by silica gel chromatography, (340 g Si), eluting with 30→80% EtOAc/cyclohexane. The appropriate fractions were combined and concentrated in vacuo to afford the title compound as a colourless oil—benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (12.75 g, 54.7 mmol, 79% yield).

1. temperaturecooled
2. customto reach rt
3. customthe layers were partitioned
4. additionThe organic layer was added dropwise to a stirred 5% aqueous solution of NaS2O5 (200 mL)
5. additionAt the end of the addition
6. stirringthe mixture was stirred for a further 1 h
7. customthe layers were separated
8. extractionthe aqueous layer was back extracted with DCM (50 mL×2)
9. washwashed with 5% aqueous K2CO3 solution (100 mL×3)
10. additionThe organics were therefore added to a stirred solution of 5% NaS2O5(aq) (200 mL)
11. stirringthe resultant biphasic mixture stirred for 1 h
12. customThe layers were separated
13. washaqueous layer washed with further DCM (2×50 mL)
14. dry with materialThe combined organics were then dried (Na2SO4)
15. concentrationand concentrated in vacuo
16. customto afford the crude product as a pale-gold oil
17. customThe crude product was purified by silica gel chromatography, (340 g Si),
18. washeluting with 30→80% EtOAc/cyclohexane
19. concentrationconcentrated in vacuo

ORD record

ord-1708c09ce8284034881e0cae8b109c64

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09127003B2