Methylphenidate + Analogs, total synthesis.

1. 2017-06-25 at 5:27 PM UTC

   #1
   

   Deprotonater Yung Blood
   I have more on the subject but I can't find anything about it in english for some reason, I will keep digging.
   
   https://www.google.com/patents/US9079928
   
   

   To a solution of protected hydroxyl acid 4 (1 mmol) in DCM (8 mL) was added TEA (2.5 mmol) and the solution was cooled down to 0° C. A solution of 4-nitrophenyl chloroformate (5, 1 mmol) in DCM (2 mL) was added drop-wise at 0° C. After the addition the reaction mixture was slowly brought to room temperature and left overnight. The solvent was evaporated and dried in vacuum to give the carbonate derivative 6. Compound 6 was dissolved in dimethylformamide (DMF) and to the solution were added TEA (3 mmol) and MPH.HCl (1.05 mmol). The mixture was heated for 8 h at 75° C. Solvent was removed under reduced pressure. The residue was dissolved in EtOAc (60 mL) and washed with 5% aq. NaHCO3 (2×40 mL) and brine (1×40 mL). The organic phase was dried over Na2SO4 and evaporated to dryness to give 8, which was purified by preparative HPLC.
   
   In other embodiments, the synthesis of MPH-CO-l-lactate (8b, A=-CH(CH3)—) is as follows:
   
   To a solution of benzyl lactate 4 (A=-CH(CH3)—; 0.39 g, 2 mmol) in DCM (8 mL) was added TEA (0.69 mL, 5 mmol) and the solution was cooled down to 0° C. A solution of 4-nitrophenyl chloroformate 5 (0.436 g, 2.1 mmol) in DCM (3 mL) was added drop-wise at 0° C. Subsequently, the reaction mixture was slowly brought to room temperature and left overnight. The solvent was evaporated in vacuum and dried to give the carbonate derivative 6 (A=-CH(CH3)—). Compound 6 was dissolved in DMF (12 mL) and to the solution were added TEA (0.84 mL, 6 mmol) and MPH.HCl (0.604 g, 2.23 mmol). The mixture was heated for 20 h at 65° C. Solvent was removed under reduced pressure. The residue was dissolved in EtOAc (40 mL) and was washed with 5% aq. NaHCO3 (2×30 mL) and brine (1×30 mL). The organic phase was dried over Na2SO4, evaporated to dryness and purified by preparative HPLC to give 8b (0.62 g).

2. 2017-06-25 at 6:03 PM UTC

   #2
   

   mashlehash victim of incest [my perspicuously dependant flavourlessness]
   Thanks for the wonderful information.