Sodium Hydroxide → m-tert-Butylbenzoic acid

Preparation C2, Step 1: A mixture of the commercially available methyl 3-bromo-5-tert-butylbenzoate (700 mg, 2.58 mMol), aqueous NaOH (1 N, 7.75 mL, 7.75 mMol), and Pearlman's catalyst (100 mg) in methanol (20 mL) was hydrogenated at 50 psi for 22 hours. The catalyst was removed by filtration and rinsed with a small amount of methanol. The filtrate was concentrated in-vacuo to remove methanol, and the aqueous mixture was acidified with 1 N HCl (10 mL), then extracted with ethyl acetate (3×20 mL). The combined organic phases were dried over sodium sulfate, then concentrated in-vacuo. Analysis of the resulting material by LC/MS showed that the ester had hydrolyzed to the carboxylic acid, but that the bromide was still present. The material was dissolved in methanol (20 mL), and hydrogenated overnight at 50 psi in the presence of 1 N aqueous NaOH (5.2 mL, 5.2 mMol) and 10% palladium on activated carbon (50 mg). Analysis of the crude reaction mixture by LC/MS showed that the bromine was still present, so Pearlman's catalyst (200 mg) was added, and hydrogenation at 50 psi was continued for 23 hours. MS showed that the reaction was now complete, so the reaction was worked up as described previously in this example to yield 376 mg (81% yield) of white powder as product. MS (AP−)=177 (M−H)

1. customThe catalyst was removed by filtration
2. washrinsed with a small amount of methanol
3. concentrationThe filtrate was concentrated in-vacuo
4. customto remove methanol
5. extractionextracted with ethyl acetate (3×20 mL)
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. concentrationconcentrated in-vacuo
8. dissolutionThe material was dissolved in methanol (20 mL)
9. customhydrogenated overnight
10. customAnalysis of the crude reaction mixture by LC/MS
11. waithydrogenation at 50 psi was continued for 23 hours

ORD record

ord-58ca286659794b549a18e6c8dbc32e69

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482335B2