Boron trifluoride → 2-Methyl-2-phenoxy-3-thiophen-2-yl-propionic Acid

Temperature

0 °C

To a solution of triethylsilane (56.4 g, 77.4 mL, 485 mmol) in 100 mL of CH2Cl2 at −20° C., boron trifluoride diethyl etherate (68.8 g, 61.5 mL, 485 mmol) was added. A solution of 3-hydroxy-2-methyl-2-phenoxy-3-thiophen-2-yl-propionic acid (45.0 g, 162 mmol) in CH2Cl2 (600 mL) was then added dropwise to the BF3 solution over 1 h, keeping the temperature at −15° C. The reaction was stirred at 0° C. for 2 h. The reaction was quenched with 1 N NaOH (approx. 360 mL) diluted with 180 mL of water and the pH was adjusted to pH=4.0 using 1 N HCl and 1 N NaOH. The organic layer was separated and the aqueous layer was further extracted with CH2Cl2 (2×300 mL). The combined organic layers were then washed with 0.1 N HCl (300 mL) and water (2×300 mL). Xylene (150 mL) and NaCl were added and the organics were concentrated to dryness to yield 40.0 g of crude product. The product was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 6.86-7.29 (m, 8 H), 3.53 (d, 2 H), 3.37 (d, 2 H), 1.44 (s, 3 H); MS (EI) 263.1 (M+H)+.

1. customat −15° C
2. customThe reaction was quenched with 1 N NaOH (approx. 360 mL)
3. additiondiluted with 180 mL of water
4. customThe organic layer was separated
5. extractionthe aqueous layer was further extracted with CH2Cl2 (2×300 mL)
6. washThe combined organic layers were then washed with 0.1 N HCl (300 mL) and water (2×300 mL)
7. additionXylene (150 mL) and NaCl were added
8. concentrationthe organics were concentrated to dryness

ORD record

ord-55509309bd09441896b3f194bc9ce9b3

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07345070B2