Bromoacetic Acid → 2-(1-(4-Chloro-3-fluorophenyl)cyclobutoxy)acetic acid

TO an ambient suspension of NaH (0.341 g, 8.52 mmol, 60% dispersion in mineral oil) in N,N-dimethylformamide (7 mL) was added a solution of Example 56A (0.342 g, 1.71 mmol) in N,N-dimethylformamide (1 mL) dropwise. The reaction was stirred for 0.5 h, and 2-bromoacetic acid (0.474 g, 3.41 mmol) was added as a solution in N,N-dimethylformamide (2 mL) dropwise. The reaction was stirred at room temperature for 24 h and was then quenched by the slow addition of H2O (10 mL) and diethyl ether (15 mL). The layers were separated, and the organic discarded. The aqueous was acidified to pH ˜4-5 with 10% HCl and was extracted with diethyl ether (3×15 mL). The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a yellow oil, which was used without further purification in the subsequent step, MS (ESI)m/z 2.59 [M+H]+.

1. stirringThe reaction was stirred at room temperature for 24 h
2. customwas then quenched by the slow addition of H2O (10 mL) and diethyl ether (15 mL)
3. customThe layers were separated
4. extractionwas extracted with diethyl ether (3×15 mL)
5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto give a yellow oil, which
9. customwas used without further purification in the subsequent step, MS (ESI)m/z 2.59 [M+H]+

ORD record

ord-41eec3801b094341b151e0d4eb5b0442

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901152B2