Hydrochloric Acid → 2-(Oxan-4-yl)propanoic acid

To a solution of (Tetrahydro-pyran-4-yl)-acetic acid ethyl ester (2.0 g, 11.6 mmol) in 50 mL of THF at −78° C. LDA (1.0 M, 17.4 mL, 34.8 mmol) is added dropwise. The solution is stirred for 0.5 h and treated with HMPA (3.2 mL, 9.3 mmol) and MeI (4.94 g, 34.8 mmol). The reaction mixture is stirred at the same temperature for 0.5 h and for 1.5 h at 0° C., acidified with aqueous 1 N aqueous HCl solution, and extracted twice with ether (2×40 mL). The organic phase is washed with saturated aqueous NaCl solution, dried (MgSO4), and concentrated in vacuo to give 1.8 g of 2-(Tetrahydro-pyran-4-yl)-propionic acid ethyl ester which is hydrolyzed without further purification. A solution of the crude ester (500 mg, 2.68 mmol) and 5 N aqueous NaOH solution (2.68 mL, 13.4 mmol) in dioxane-water (4 mL/2 mL) is heated at 60° C. for 2 h. The solution is cooled to room temperature, acidified with 1 N aqueous HCl solution, and extracted with ether. The ether layer is washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and concentrated in vacuo to give 400 mg of the title compound. MS: 159 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 2 min then 100% CH3CN+0.1% TFA for 1 min, flow 0.5 ml/min): 1.27 min.

1. customis hydrolyzed without further purification
2. extractionextracted with ether
3. washThe ether layer is washed with saturated aqueous NaCl solution
4. dry with materialdried over anhydrous MgSO4
5. concentrationconcentrated in vacuo

ORD record

ord-86335c07dbc44fd3827a8206ffa7dc7f

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163773B2