Hydrochloric Acid → 4-(1,4-Oxazepan-4-yl)cyclohexanone

To a cooled (<15° C.) solution of 8 (10.31 g, 42.75 mmol) in THF (216 mL) was added 7 N aqueous HCl (86 mL, 0.602 mol) over a period of 5 min. Cooling bath was then removed and the reaction mixture was stirred overnight at r.t. Then, the reaction mixture was basified to pH 8 by dropwise addition of 50% aqueous NaOH (48 g, 0.602 mol) over a period of 30 min while maintaining the internal temperature at 10-13° C. using an external cooling bath (0° C.). Hexane (50 mL) was added and the organic layer was separated, dried over MgSO4 and concentrated to afford yellowish liquid (7.21 g). The aqueous layer was extracted with EtOAc (4×50 mL). The extracts were combined, dried (MgSO4) and concentrated to afford the second portion of crude product (1.58 g). Both portions of crude product were combined and distilled in vacuum to afford ketone (VII-h) (7.27 g, 86%) as colorless liquid b.p. 98° C./5.3·10−3 mbar; 1H NMR (400 MHz, CDCl3) δ 1.73-1.85 (m, 2H), 1.89 (quintet, J=5.9 Hz, 2H), 2.05-2.15 (m, 2H), 2.30-2.42 (m, 2H), 2.43-2.52 (m, 2H), 2.79-2.85 (m, 4H), 3.03 (tt, J=10.4, 6.6 Hz, 1H), 3.72-3.77 (m, 2H), 3.82 (t, J=6.0 Hz, 2H).

1. temperatureCooling bath
2. customwas then removed
3. temperaturewhile maintaining the internal temperature at 10-13° C.
4. custom(0° C.)
5. customthe organic layer was separated
6. dry with materialdried over MgSO4
7. concentrationconcentrated

ORD record

ord-5b82b15ba48f4b859593b61cd9660ad4

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178552B2