Processes for the preparation of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and N-methyl-1,3-benzodioxolylbutanamine (MBDB)

A process for preparing a compound of Formula (R)-I or (S)-I:

• wherein
• R is selected from CH3 and CH2CH3;
• the process comprising:
• protecting the amino group of 3,4-dihydroxy-L-phenylalanine (L-DOPA) C1-4alkyl ester of Formula (S)-A, or the amino group of 3,4-dihydroxy-D-phenylalanine (D-DOPA) C1-4alkyl ester of Formula (R)-A:
• wherein R1 is C1-4alkyl,
• with a C1-4alkoxycarbonyl protecting group or a benzyloxy carbonyl protecting group to provide a compound of Formula (S)-B or (R)-B, respectively:
• wherein
• R1 is C1-4alkyl, and
• R2 is C1-4alkyl or CH2Ph;
• cyclizing the compound of Formula (S)-B or (R)-B to provide a compound of Formula (S)-C or (R)-C, respectively:
• wherein
• R1 is C1-4alkyl, and
• R2 is C1-4alkyl or CH2Ph;
• reacting the compound of Formula (S)-C or (R)-C with a reducing agent to provide a compound of Formula (S)-D or (R)-D, respectively:
• wherein R2 is C1-4alkyl or CH2Ph;
• when R is CH2CH3, further oxidizing the compound of Formula (S)-D or (R)-D to provide a compound of Formula (S)-Dox or (R)-Dox, respectively;
• and
• wherein R2 is C1-4alkyl or CH2Ph;
• reacting the compound of Formula (S)-Dox or (R)-Dox with a methyl organometallic reagent to provide the compound of Formula (S)-D′ or (R)-D′, respectively;
• wherein R2 is C1-4alkyl or CH2Ph;
• and
• reacting the compound of Formula (S)-D or (R)-D with a chlorinating agent to provide a compound of Formula (S)-E or (R)-E, respectively, or reacting the compound Formula of(S)-D′ or (R)-D′ with a chlorinating agent to provide a compound of Formula (S)-E′ or (R)-E′, respectively:
• wherein R2 is C1-4alkyl or CH2Ph;
• or
• when R is CH2CH3, hydrolyzing the compound of Formula (S)-C or (R)-C to provide the compound of Formula (S)-C′ or (R)-C′, respectively;
• wherein R2 is C1-4alkyl or CH2Ph;
• and
• converting the compound of Formula (S)-C′ or (R)-C′ to the compound of Formula (S)-E″ or (R)-E″, respectively
• wherein R2 is C1-4alkyl or CH2Ph;
• and
• reacting the compound of Formula (S)-E or (R)-E with a reducing agent to provide the compound of Formula (R)-I or (S)-I, respectively, wherein R is CH3,
• reacting the compound of Formula (S)-E′ or (R)-E′ with a reducing agent to provide the compound of Formula (R)-I or (S)-I, respectively, wherein R is CH2CH3, or
• reacting the compound of Formula (S)-E″ or (R)-E″ with a reducing agent to provide the compound of Formula (R)-I or (S)-I, respectively, wherein R is CH2CH3.