Sodium Hydroxide → HCID 66685725, compound

Temperature

0 °C

A solution of (1-(4-chlorophenyl)cyclobutyl)methanol (1.5 g, 7.63 mmol) in toluene (21 mL) was cooled to 0° C. and treated with a 33% aq. NaOH solution (7.43 mL) followed by tetrabutylammonium hydrogen sulfate (647 mg, 1.91 mmol). The mixture was stirred at 0° C. for 10 min and tert-butyl bromoacetate (1.11 mL, 7.63 mmol) was added. The ice bath was removed, and stirring was continued at room temperature for 50 min. Additional tert-butyl bromoacetate (1.11 mL, 7.63 mmol) was added and the mixture was stirred at room temperature for 16 h. Additional tert-butyl bromoacetate (1.11 mL, 7.63 mmol) was added and the mixture was stirred at room temperature for additional 24 h. The reaction mixture was diluted with EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), and concentrated. The crude oil was chromatographed on silica gel (Teledyne-Isco RediSep 80 g silica gel column) and eluted with hexanes, followed by 1% and 2% EtOAc in hexanes to obtain tert-butyl 2-((1-(4-chlorophenyl)cyclobutyl)methoxy)acetate (1.77 g, 75% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ ppm 7.25-7.28 (2 H, m), 7.06-7.19 (2 H, m), 3.85 (2 H, s), 3.64 (2 H, s), 2.22-2.49 (4 H, m), 1.98-2.18 (1 H, m), 1.73-1.93 (1 H, m), 1.45 (9 H, s).

1. customThe ice bath was removed
2. stirringstirring
3. waitwas continued at room temperature for 50 min
4. stirringthe mixture was stirred at room temperature for 16 h
5. stirringthe mixture was stirred at room temperature for additional 24 h
6. customThe organic layer was separated
7. washwashed with water, brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customThe crude oil was chromatographed on silica gel (Teledyne-Isco RediSep 80 g silica gel column)
11. washeluted with hexanes

ORD record

ord-5be5074b088a41d7a9083aab0275594d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187437B2