反应详情

To an ice cold solution of 0.44 g (1.4 mmol) of 4-(4-hydroxy-butyl)-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl ester in 5 ml of acetonitrile:water (1:1) was added 0.043 g (0.3 mmol) TEMPO and 0.97 g (3.0 mmol) of (diacetoxyiodo)benzene. The mixture was stirred allowed to reach room temperature and was stirred for a further 3 h after which time it was evaporated to dryness. The crude residue was redissolved in 5 ml of DMF, 0.68 g (2 mmol) of HATU and 0.6 ml (4.0 mmol) of triethylamine added followed by addition of 0.25 g (2.0 mmol) of (S)-6-aza-spiro[2.5]octan-4-ol. hydrochloride (intermediate 2). The reaction was stirred for 16 h after which time the mixture was poured onto sat. aq. NaHCO3, extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated. Purification on a SiO2-column (CH2Cl2/MeOH 95:5), afforded the titled compound in 55% yield as a colorless foam. MS: 444.3 (MH+).

1. customto reach room temperature
2. stirringwas stirred for a further 3 h after which time it
3. customwas evaporated to dryness
4. dissolutionThe crude residue was redissolved in 5 ml of DMF
5. stirringThe reaction was stirred for 16 h after which time the mixture
6. extractionextracted with EtOAc
7. washThe combined organic phases were washed with brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customPurification on a SiO2-column (CH2Cl2/MeOH 95:5)