Hydrochloric Acid → 4-(3-Hydroxyoxetan-3-yl)benzoic acid

To 4-bromobenzoic acid (434 mg, 2.16 mmol) in THF (9 mL) at −78° C. was added dropwise n-butyllithium (2.84 mL of 1.6 M in hexanes, 4.54 mmol). The reaction mixture was stirred for 30 minutes, then oxetan-3-one (218 mg, 3.03 mmol) in THF (1 mL) was added dropwise. The reaction mixture was stirred for 30 minutes at −78° C. and allowed to warm to room temperature over 30 minutes. The reaction mixture was diluted with ethyl acetate (15 mL) and acidified to pH 2 with 2 N HCl. The layers were separated and the aqueous was re-extracted with ethyl acetate (15 mL). The combined organics were washed with brine solution (10 mL), dried over MgSO4 and concentrated in vacuo to give a white solid as a 1:1 mixture of 4-(3-hydroxyoxetan-3-yl)benzoic acid/benzoic acid (380 mg, 91%).

1. stirringThe reaction mixture was stirred for 30 minutes at −78° C.
2. customThe layers were separated
3. extractionthe aqueous was re-extracted with ethyl acetate (15 mL)
4. washThe combined organics were washed with brine solution (10 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customto give a white solid

ORD record

ord-b5c6c531afde4daf91cca9310ea43501

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181273B2