Hydrochloric Acid → HCID 25019181, compound

To a stirred solution of ethyl 4-hydroxybenzoate (2.493 g, 15.0 mmol) and potassium carbonate (4.15 g, 30 mmol) in 60 mL of 2-butanone at ambient temperature was added in one portion of (bromomethyl)cyclobutane (97% pure) (2.53 g, 16.5 mmol). The stirred reaction mixture was heated at reflux for 16 hr. HPLC revealed the disappearance of the starting material of ethyl 4-hydroxybenzoate. The mixture was allowed to cool to ambient temperature. The solid was filtered off. The filter cake was washed with acetone. The combined filtrate was concentrated in vacuo to nearly dryness. Methanol was added (10 mL) was added to the residue, followed by the addition of a 2-N aqueous solution of NaOH (30 mL, 60 mmol). The reaction was stirred overnight at about 40° C. HPLC indicated that the saponification was completed, and revealed one single peak signal of the expected carboxylic acid. The reaction mixture was subjected to roto-vaporation to remove methanol. Ice was added to the basic aqueous solution. The acidification with a 35 mL of HCl aqueous 2N solution (70 mmol) led to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane. The collected solid was dried in vacuo for two days at ambient temperature to afford 2.63 g (85%) of 4-(cyclobutylmethoxy)benzoic acid as a white solid.

1. customThe stirred reaction mixture
2. temperaturewas heated
3. temperatureat reflux for 16 hr
4. filtrationThe solid was filtered off
5. washThe filter cake was washed with acetone
6. concentrationThe combined filtrate was concentrated in vacuo to nearly dryness
7. additionMethanol was added (10 mL)
8. additionwas added to the residue
9. customto remove methanol
10. additionIce was added to the basic aqueous solution
11. stirringStirring
12. waitwas continued for an additional 30 min
13. customthe precipitation
14. filtrationwas filtered off with suction through a sintered glass funnel
15. washThe collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane
16. customThe collected solid was dried in vacuo for two days at ambient temperature

ORD record

ord-4490606202ad4b26a71da8e06702ab9d

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383852B2