1-Naphthol → Ethyl 2-cyclopropyl-2-(1-naphthalenyloxy)acetate

To a solution of 1-naphthol (170 mg, 1.18 mmol) in anhydrous DMF (10 mL) was added K2CO3 (510 mg, 3.53 mmol) and ethyl α-bromocyclopropaneacetate (295 mg, 1.41 mmol). The mixture was stirred at room temperature for 2 h and then diluted with water (50 mL) and then extracted with ethyl acetate (3×50 mL). The organic extracts were combined, washed with brine, dried over anhydrous MgSO4, filtered, concentrated in vacuo and purified by flash column chromatography using a mixture of ethyl acetate and n-hexane (1:9) to furnish ethyl 2-cyclopropyl-2-(1-naphthalenyloxy)acetate (8, R=c-Pr, 296 mg, 93%) as a white solid. The ester (250 mg, 0.92 mmol) was dissolved in 20 mL THF: H2O (2:1) and then 3M NaOH (111 mg, 2.77 mmol) was added. The reaction was heated at 80° C. for 6 h. After cooling, the reaction mixture was quenched with 1N HCL to a pH ˜7 and then extracted with chloroform. The organic extract was dried over anhydrous MgSO4, filtered, concentrated in vacuo and purified by flash column chromatography eluting with a mixture of ethyl acetate/n-hexane (a gradient of 2:1) to furnish 2-cyclopropyl-2-(1-naphthalenyloxy)acetic acid (41, R=c-Pr) (136 mg, 61%) as a white solid.

1. extractionextracted with ethyl acetate (3×50 mL)
2. washwashed with brine
3. dry with materialdried over anhydrous MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. custompurified by flash column chromatography
7. additiona mixture of ethyl acetate and n-hexane (1:9)

ORD record

ord-c0ab71d80dad4c75a45c7ca249c85703

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969342B2