Hydrochloric Acid → HCID 69978605, compound

Participants

Reaction Conditions

Reaction Steps

4-(Methoxy)benzenesulfonyl chloride was dissolved in CH2Cl2 and chilled in an ice bath to 0° C. To this solution was added the hydrochloride of Pro-Phe-OMe (1 eq.) and TEA (2.2 eq). The reaction was allowed to warm to room temperature and stirred overnight under a stream of N2. The reaction mixture was then concentrated and the residue taken up in EtOAc and H2O and the organic phase was washed with sat. NaHCO3 and brine, dried (MgSO4), filtered, concentrated to a tacky solid and used without further purification. The solid product was treated with BBr3 (1M in CH2Cl2, 3.0 eq., −78° C. for one hour then warmed to rt). The reaction was then chilled in an ice bath and quenched with water. Following concentration, the residue was taken-up in EtOAc and water. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to a foam. The product was esterified with MeOH and HCl gas (0° C. to rt, 16 hours) and purified by column chromatography. This product was then added to a chilled (0° C.) THF solution of triphenylphosphine (1.10 eq), 3-dimethylmino-1-propanol (1.0 eq) and diethyl azodicarboxylate (1.10 eq). The reaction temperature was held at 0° C. for 30 minutes and then allowed to warm to room tempetature and stirred overnight. The reaction mixture was concentrated and taken-up in EtOAc and washed with sat. NaHCO3. The product was than extracted with 0.2 N citric acid, and the aqueous phase washed with EtOAc. The aqueous phase was then made basic with solid NaHCO3 and the product extracted with EtOAc. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated. The product was purified by preparative TLC. The hydrolysis was performed using Method 7 to yield the title compound as a mixture of diastereomers and was isolated as a white, hygroscopic solid.

Provenance & Evidence