Acetic Acid → HCID 118179072, compound

Participants

Reaction Conditions

Reaction Steps

8.7 g (18.6 mmol) of the compound from Example 2A were stirred in 90 ml of a 33% strength solution of hydrogen bromide in glacial acetic acid under reflux overnight. After addition of another 90 ml of hydrogen bromide solution, the mixture was stirred at a bath temperature of 135° C. for a further night. The mixture was then concentrated under reduced pressure, another 40 ml of the solution of hydrogen bromide in glacial acetic acid were added to the residue and the mixture was stirred at a bath temperature of 110° C. for another night. The mixture was then once more concentrated to dryness. The residue, which comprised 77% of the dicarboxylic acid compound 5-{(4-carboxybutyl) [2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid [LC-MS (Method 2): Rt=0.64 min; MS (ESIpos): m/z=412 [M+H]+], was subjected to incipient dissolution in 190 ml of ethanol, and 1.65 ml of thionyl chloride were added dropwise. The mixture was stirred at 70° C. overnight and then concentrated under reduced pressure. The residue (about 13 g) was taken up in ethyl acetate and washed twice with dilute aqueous sodium carbonate solution. The organic phase was dried over sodium sulphate and concentrated. The crude product (8.8 g) was purified by flash chromatography on silica gel using the mobile phase cyclohexane/ethyl acetate 5:1.

Provenance & Evidence