Sodium Bicarbonate → 1,1-Dimethylethyl cyclopropanepropanoate

Temperature

0 °C

To a cool (0° C., precooled for at least 15 min), stirred solution of 3-cyclopropylpropanoic acid (5 g, 43.8 mmol) in hexane (30.0 mL) and THF (30 mL) under N2 was added tert-butyl 2,2,2-trichloroacetimidate (15.7 mL, 88 mmol) portion wise over 5 min. The reaction mixture was stirred for 15 min. Boron trifluoride ether complex (0.555 mL, 4.38 mmol) was added and the reaction mixture was allowed to warm to room temperature as the bath warmed overnight. To the clear reaction mixture was added NaHCO3 (5 g) and stirred for 60 min. The suspension was filtered through MgSO4 and washed with 300 mL hexane. The filtrate was allowed to sit, then the resulting solid was filtered through the same MgSO4 filter, washed with hexane (100 mL). The filtrate was concentrated under vacuo with the water bath not turned on. The residue was purified by silica gel chromatography (hexanes/EtOAc) to provide Intermediate S1B (6.05 g, 81%) as clear oil: 1H NMR (400 MHz, CDCl3) δ 2.29 (2H, t, J=7.48 Hz), 1.35-1.54 (11H, m), 0.60-0.75 (1H, m), 0.29-0.46 (2H, m), −0.06-0.10 (2H, m).

1. additionBoron trifluoride ether complex (0.555 mL, 4.38 mmol) was added
2. temperatureto warm to room temperature as the bath
3. temperaturewarmed overnight
4. stirringstirred for 60 min
5. filtrationThe suspension was filtered through MgSO4
6. washwashed with 300 mL hexane
7. filtrationthe resulting solid was filtered through the same MgSO4
8. filtrationfilter
9. washwashed with hexane (100 mL)
10. concentrationThe filtrate was concentrated under vacuo with the water bath not
11. customThe residue was purified by silica gel chromatography (hexanes/EtOAc)
12. customto provide Intermediate S1B (6.05 g, 81%) as clear oil

ORD record

ord-305deaf9778941b4bf5a84ae96ae1ac2

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242941B2