N-Acetyl-DL-cysteine → 5-(2-Acetylamino-3-mercapto-propionylamino)-2-hydroxy-benzoic acid

Temperature

0 °C

To the solution of 2-acetylamino-3-mercapto-propionic acid (3.0 mmol) in 50 mL of dimethylformamide, hydroxybenzotriazole (3.3 mmol) and DCC (3.3 mmol) were added with stirring at 0°C. for 1 h. To the reaction mixture, 4 or 5-amino-2-tert-butoxy-benzoic acid tert-butyl ester (3) (3.0 mmol) was added and stirred mechanically for 3 h at 0°C. and 72 h at room temperature. After filtration, the filtrate was evaporated under reduced pressure to remove the solvent. The oily residue thus obtained was dissolved in ethyl acetate; the organic layer washed with brine, dried on anhydrous MgSO4, filtered and the solvent evaporated. The crude intermediate 4 was treated with a solution of TFA (40%) in CH2Cl2. After 2 h the solvent was removed to obtain compound (5) as a crude residue. The residue was loaded on a silica gel open column and eluted with CH2Cl2/MeOH (8/2), from which 4 or 5-(2-Acetylamino-3-mercapto-propionylamino)-2-hydroxy-benzoic acid (5), compound of Formula XI, was obtained (78% yield).

1. stirringstirred mechanically for 3 h at 0°C. and 72 h at room temperature
2. filtrationAfter filtration
3. customthe filtrate was evaporated under reduced pressure
4. customto remove the solvent
5. customThe oily residue thus obtained
6. washthe organic layer washed with brine
7. dry with materialdried on anhydrous MgSO4
8. filtrationfiltered
9. customthe solvent evaporated
10. additionThe crude intermediate 4 was treated with a solution of TFA (40%) in CH2Cl2
11. customAfter 2 h the solvent was removed

ORD record

ord-4a5283155c7343ffbe19bb6f560a263a

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07498355B2