A method for synthesizing levomethadone hydrochloride including producing (R)-2-(dimethylamino)propan-1-ol by reducing N,N-dimethyl-D-alanine using borax, forming (R)-1-chloro-N,N-dimethylpropane-2-amine hydrochloride by chlorinating the (R)-2-(dimethylamino)propan-1-ol, synthesizing levomethadone nitrile hydrochloride by mixing the (R)-1-chloro-N,N-dimethylpropane-2-amine and diphenylacetonitrile with potassium t-butoxide and producing levomethadone hydrochloride by exposing the levomethadone nitrile hydrochloride to a Grignard reagent.

A method for synthesizing levomethadone hydrochloride including producing (R)-2-(dimethylamino)propan-1-ol by reducing N,N-dimethyl-D-alanine using borax, forming (R)-1-chloro-N,N-dimethylpropane-2-amine hydrochloride by chlorinating the (R)-2-(dimethylamino)propan-1-ol, synthesizing levomethadone nitrile hydrochloride by mixing the (R)-1-chloro-N,N-dimethylpropane-2-amine and diphenylacetonitrile with potassium t-butoxide and producing levomethadone hydrochloride by exposing the levomethadone nitrile hydrochloride to a Grignard reagent.

In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions.

In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions.

In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions.

The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound.

The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound.

The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound.

The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture including a base, the base comprising a carbonate salt, a phosphate salt or an acetate salt, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound in the presence of a mild base.

The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture including a base, the base comprising a carbonate salt, a phosphate salt or an acetate salt, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound in the presence of a mild base.