Sodium Hydroxide → 1-(Cyanomethyl)cyclobutane-1-carboxylic acid

To a stirred solution of Intermediate 220B (0.110 g, 0.658 mmol) in ethanol (3.5 mL), THF (3.5 mL) and water (3 mL) was added NaOH (0.079 g, 1.974 mmol) and the reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated and the residue was diluted with water (3 mL) and extracted with EtOAc (3×20 mL) The pH of the aqueous layer was adjusted to 3 using a 1.5N aqueous solution of HCl and extracted with EtOAc (3×10 mL). The combined organic layer was washed with water, dried over Na2SO4, filtered and the filtrate concentrated. The residual mass was then azeotroped with toluene to obtain the Intermediate 220C as a brown oil (0.06 g, 66% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.65 (br. s., 1H), 3.04-2.79 (m, 2H), 2.42-2.17 (m, 2H), 2.09-1.67 (m, 4H).

1. concentrationThe reaction mixture was concentrated
2. additionthe residue was diluted with water (3 mL)
3. extractionextracted with EtOAc (3×20 mL) The pH of the aqueous layer
4. extractionextracted with EtOAc (3×10 mL)
5. washThe combined organic layer was washed with water
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationthe filtrate concentrated
9. customThe residual mass was then azeotroped with toluene

ORD record

ord-702d2d3feef943f3b6695821cc7c1321

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2