Bromoacetic Acid → 2-(1-(4-Bromo-2-fluorophenyl)cyclobutoxy)acetic acid

Temperature

22 °C

A 50 mL round-bottomed flask was charged with NaH (361 mg, 9.04 mmol) and N,N-dimethylacetamide (5 mL). A solution of the product from Example 60A (443 mg, 1.808 mmol) in N,N-dimethylacetamide (5 mL) was added dropwise, and the reaction was stirred at 22° C. for 30 min. A solution of 2-bromoacetic acid (502 mg, 3.62 mmol) in N,N-dimethylacetamide (5 mL) was added dropwise. The reaction was stirred at 22° C. for 16 hours and was then quenched by the slow addition of water (15 mL). The aqueous was extracted with 1:1 diethyl ether/hexanes (2×20 mL), and the organics discarded. The aqueous layer was acidified to pH 1 with 1M HQ and extracted with ethyl acetate (2×75 mL). The combined organics were washed with water (4×20 mL) and brine (1×20 mL), dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.54-1.70 (m, 1H), 1.91-2.10 (m, 1H), 2.34-2.47 (m, 4H), 3.65 (s, 2H), 7.34-7.43 (m, 2H), 7.49-7.53 (m 1H), 12.45 (s, 1H).

1. stirringThe reaction was stirred at 22° C. for 16 hours
2. customwas then quenched by the slow addition of water (15 mL)
3. extractionThe aqueous was extracted with 1:1 diethyl ether/hexanes (2×20 mL)
4. extractionextracted with ethyl acetate (2×75 mL)
5. washThe combined organics were washed with water (4×20 mL) and brine (1×20 mL)
6. dry with materialdried with anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-495512587d1a44f9b525b9559859b2bc

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242139B2