Hydrochloric Acid → 4-Aza-spiro[2.5]octane-4-carbonyl chloride

Temperature

0 °C

To a vigorously stirred pale yellow solution of 4-azaspiro[2,5]octane hydrochloride (ABCR, 443 mg, 3.00 mmol), pyridine (0.36 mL, 4.5 mmol) and DIPEA (0.52 mL, 3.0 mmol) in DCM (10 mL) at 0° C. was added a solution of triphosgene (594 mg, 2.00 mmol) in DCM (5 mL) dropwise over 5 min. The resulting orange solution was stirred at 0° C. for 30 min, and at RT for 66 h. Aq. HCl solution (1M, 15 mL) was added and the mixture stirred for 30 min. The aqueous was extracted with DCM (4×15 mL), then the combined organics passed through a hydrophobic frit and concentrated in vacuo to leave the title compound as a red-brown oil (100% yield). 1H NMR (300 MHz, CDCl3): ˜2:1 ratio of rotamers, 0.71-0.76 (1.33H, m), 0.82 (0.67H, br s), 1.00-1.04 (1.33H, m), 1.09 (0.67H, br s), 1.53-1.59 (2H, m), 1.64-1.72 (2H, m), 1.75-1.83 (2H, m), 3.61-3.74 (2H, m).

1. waitat RT for 66 h
2. stirringthe mixture stirred for 30 min
3. extractionThe aqueous was extracted with DCM (4×15 mL)
4. concentrationconcentrated in vacuo

ORD record

ord-3849fff5b7fc4713b81e929404a637b8

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139584B2