Methanol → (1-{4-[4-(2-Benzyloxycarbamoyl-ethyl)-phenoxy]-benzyl}-2-morpholin-4-yl-2-oxoethyl)-carbamic acid tert-butyl ester

Temperature

2.5 °C

The compound 19 (1.95 g, 3.61 mmol) was dissolved in dry DMF (30 mL) and cooled to 0-5° C. 1-Hydroxybenzotriazole (0.54 g, 4.0 mmol), EDCI (0.7 g, 3.61 mmol), and triethylamine (1.5 mL, 11.0 mmol) were added to the above mixture followed by stirring for 15 min. O-Benzylhydroxylamine hydrochloride (0.64 g, 4.0 mmol) was added and the mixture was allowed to come to room temperature and stirred for 18 h. The solvent was evaporated under reduced pressure and the residual oil was taken up in EtOAc (60 mL). The organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×40 mL). The resulting EtOAc layer was dried and concentrated to yield the crude product. Silica gel flash chromatography (CHCl3:MeOH—49:1) yielded the desired benzyl hydroxamate 15 (1.0 g, 44%). 1H NMR (400 MHz, DMSO-d6): 10.93 (s, 1H), 8.23 (s, 1H), 7.28-7.33 (m, 5H), 7.20 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H), 6.84 (d, J=7.2 Hz, 2H), 6.80 (d, J=8.4 Hz, 2H), 4.69 (s, 2H), 4.02 (m, 1H), 3.07-3.42 (m, 8H), 2.60-2.85 (m, 4H), 2.21 (t, J=7.6 Hz, 2H), 1.97 (s, 3H), 1.28 (s, 9H).

1. customto come to room temperature
2. stirringstirred for 18 h
3. customThe solvent was evaporated under reduced pressure
4. extractionThe organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×40 mL)
5. dry with materialThe resulting EtOAc layer was dried
6. concentrationconcentrated
7. customto yield the crude product

ORD record

ord-eaaaa610733f4470bb10caca609f6e79

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07399786B2