METHODS OF MANUFACTURE OF R-MDMA

1 . A method of manufacturing R-MDMA, by the steps shown in FIG. 3 , including the steps of:

forming a Grignard reagent from 5-bromobenzodioxole;

treating the Grignard reagent with S-propylene oxide to form chirally pure alcohol (S)-1-(benzo[d][1,3]dioxol-5-yl)propan-2-ol (1);

activating the alcohol as mesylate (S)-1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl methanesulfonate (2);

converting the mesylate to chirally pure azide ((R)-5-(2-azidopropyl)benzo[d][1,3]dioxole) (3);

reducing the azide to amine (R)-1-(benzo[d][1,3]dioxol-5-yl)propan-2-amine (4);

protecting the amine as ethyl (R)-(1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl)carbamate (5);

reducing the protected amine to yield R-MDMA free base ((R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine) (6); and

treating the free base with an acid to form a salt of (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine in >99% enantiomeric excess.

2 . The method of claim 1 , wherein said protecting step is further defined as protecting the amine with a compound chosen from the group consisting of di-tert-butyl dicarbonate and ethyl chloroformate.

3 . The method of claim 1 , wherein said reducing step is further defined as reducing the protected amine 5 with LiAlH 4 .

4 . The method of claim 1 , wherein said salt formed in said treating step is chosen from the group consisting of hydrochloride, hydrobromide, maleate, L-malate, D-tartrate, meso-tartrate, citrate, phosphate, naphthylene-1,5-disulphonate, fumarate, sulfate, mesylate, acetate, and oxalate.

5 . The method of claim 1 , wherein said method provides at least 30% overall yield of R-MDMA.

6 . The method of claim 1 , further including the step of converting the amine 4 to a salt for purification or storage.

7 . The method of claim 6 , wherein the salt is (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine hydrochloride (7).

8 . A method of manufacturing S-MDMA, by the steps shown in FIG. 4 , including the steps of:

forming a Grignard reagent from 5-bromobenzodioxole;

treating the Grignard reagent with R-propylene oxide to form chirally pure (R)-1-(benzo[d][1,3]dioxol-5-yl)propan-2-ol (8);

activating the alcohol (8) as mesylate (R)-1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl methanesulfonate (9);

converting the mesylate (9) to chirally pure azide ((S)-5-(2-azidopropyl)benzo[d][1,3]dioxole) (10);

reducing the azide (10) to amine (S)-1-(benzo[d][1,3]dioxol-5-yl)propan-2-amine (11);

protecting the amine (11) with di-tert-butyl dicarbonate as ethyl (S)-(1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl)carbamate (12);

reducing the protected amine (12) to yield S-MDMA free base ((S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine) (13); and

treating with an acid to form a salt of (S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine in >99% enantiomeric excess.

9 . The method of claim 8 , wherein said protecting step is further defined as protecting the amine with a compound chosen from the group consisting of di-tert-butyl dicarbonate and ethyl chloroformate.

10 . The method of claim 8 , wherein said reducing step is further defined as reducing the protected amine 5 with LiAlH 4 .

11 . The method of claim 8 , wherein said salt formed in said treating step is chosen from the group consisting of hydrochloride, hydrobromide, maleate, L-malate, D-tartrate, meso-tartrate, citrate, phosphate, naphthylene-1,5-disulphonate, fumarate, sulfate, mesylate, acetate, and oxalate.

12 . The method of claim 8 , wherein said method provides at least 30% overall yield of S-MDMA.

13 . The method of claim 8 , further including the step of converting the amine 11 to a salt for purification or storage.

14 . The method of claim 13 , wherein the salt is (S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine hydrochloride (14).