Triphenylphosphine → 4-Benzyl-1,4-diazabicyclo[3.2.1]octane

Diethyl azodicarboxylate (15.8 mL, 100 mmol) was slowly added to a solution of triphenylphosphine (26.2 g, 100 mmol) in THF (200 mL) while maintaining the reaction temperature below 20° C. After stirring this mixture for 30 min at RT, a solution of 2-(1-benzyl-piperazine-2-yl)-ethanol (11 g, 50 mmol) in THF (100 mL) was added while maintaining the reaction temperature below 20° C. The reaction mixture became turbid and the solvent was removed in vacuo after a period of 1 h. The residue was partitioned between water (20 mL) and ethyl acetate (50 mL) and the pH was adjusted to 2 with 6 N HCl. The phases were separated and the aqueous phase was extracted with EtOAc (50 mL) at pH 3.0, 4.5 and 10 (4×). The pH 10 extracts were combined, dried (Na2SO4), filtered and concentrated to an oil. The oil was triturated three times with hot hexanes (100 mL) to remove any remaining triphenylphosphine and triphenylphosphine oxide and the hexanes were decanted. The remaining oil was dried resulting in 7.5 g (74%) of the title compound: APCI MS m/z 203.2 (M+1).

1. temperaturewhile maintaining the reaction temperature below 20° C
2. temperaturewhile maintaining the reaction temperature below 20° C
3. customthe solvent was removed in vacuo after a period of 1 h
4. customThe residue was partitioned between water (20 mL) and ethyl acetate (50 mL)
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with EtOAc (50 mL) at pH 3.0, 4.5 and 10 (4×)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated to an oil
10. customThe oil was triturated three times with hot hexanes (100 mL)
11. customto remove any remaining triphenylphosphine and triphenylphosphine oxide
12. customthe hexanes were decanted
13. customThe remaining oil was dried

ORD record

ord-b18290aaca1742949fa7c77fe05c394f

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07442694B2