I haven't seen any attempts on here so I figured I'd throw in some info.
Reaction conditions: 2g ketone
All reactants in molar equivalence to ketone
Formation of NaBH(OAc)3
1.5 equiv of NaBH4 is added to 25mL of EtOAc1 on an ice bath which was previously dried over anhydrous sodium sulfate. This forms a suspension which does not dissolve and does not produce noticeable hydrogen evolution. 4.5 equiv of glacial acetic acid is added in one portion with vigorous evolution of hydrogen. On larger scales this should probably be done piece meal to prevent excessive heating. This solution is allowed to stir for approximately ten to twenty minutes. Depending on the quality/age of the NaBH4, the suspension will disppear and turn into a solution after this time.2
Preparation of imine
While the sodium acetoxyborohydride is forming, 2gr of MDP2P is aded to 1.5g (14.5mmol, 1.3 equiv) of 33% solution of MeNH2 in anhydrous ethanol on an ice bath and the solution is stirred by hand until the sodium acetoxyborohydride is prepared.
Reaction
At this time, the methylamine/MDP2P solution is added in one portion to the NaBH(OAc)3 and the solution is stirred for 12 hours. TLC at 1 hour shows significant disappearance of starting material. TLC at 12 hours indicates a small amount of starting material present.
Work up
The residual hydride (and there is quite a bit left) is quenched by slow addition of water until bubbling subsides. The impatient chemist will squirt in 1M HCl on a small scale without noticeable heat. Do not attempt to work up until bubbling has completely subsided. Transfer to a sep funnel, basify to pH of 12 with 1M NaOH.3 Retain organic layer and extract aq. layer 2-3x with DCM4. Separation is slow after shaking. Combine organic layers, extract 3x with 1M HCl. MDMA.HCl in aqueous layer, proceed from here however you'd like.
Yield over 2 trials was 72% and 82% of citrate salt. Higher yields are most likely possible by extending reaction time or using higher excess of NaBH(OAc)3 and quenching earlier.
1 The reaction has been performed in 1,2-DCE without a noticeable change in yield.
2 No noticeable difference in yield has been found based on the complete dissolution of the suspension
3 Do not attempt to wash the initially acidic aq. layer, you will lose a significant amount of product for the obvious reasons.
4 DCM was tried, as well as EtOAc and CHCl3. CHCl3 gave best separation (no emulsion etc) but DCM was most practical
Reaction conditions: 2g ketone
All reactants in molar equivalence to ketone
Formation of NaBH(OAc)3
1.5 equiv of NaBH4 is added to 25mL of EtOAc1 on an ice bath which was previously dried over anhydrous sodium sulfate. This forms a suspension which does not dissolve and does not produce noticeable hydrogen evolution. 4.5 equiv of glacial acetic acid is added in one portion with vigorous evolution of hydrogen. On larger scales this should probably be done piece meal to prevent excessive heating. This solution is allowed to stir for approximately ten to twenty minutes. Depending on the quality/age of the NaBH4, the suspension will disppear and turn into a solution after this time.2
Preparation of imine
While the sodium acetoxyborohydride is forming, 2gr of MDP2P is aded to 1.5g (14.5mmol, 1.3 equiv) of 33% solution of MeNH2 in anhydrous ethanol on an ice bath and the solution is stirred by hand until the sodium acetoxyborohydride is prepared.
Reaction
At this time, the methylamine/MDP2P solution is added in one portion to the NaBH(OAc)3 and the solution is stirred for 12 hours. TLC at 1 hour shows significant disappearance of starting material. TLC at 12 hours indicates a small amount of starting material present.
Work up
The residual hydride (and there is quite a bit left) is quenched by slow addition of water until bubbling subsides. The impatient chemist will squirt in 1M HCl on a small scale without noticeable heat. Do not attempt to work up until bubbling has completely subsided. Transfer to a sep funnel, basify to pH of 12 with 1M NaOH.3 Retain organic layer and extract aq. layer 2-3x with DCM4. Separation is slow after shaking. Combine organic layers, extract 3x with 1M HCl. MDMA.HCl in aqueous layer, proceed from here however you'd like.
Yield over 2 trials was 72% and 82% of citrate salt. Higher yields are most likely possible by extending reaction time or using higher excess of NaBH(OAc)3 and quenching earlier.
1 The reaction has been performed in 1,2-DCE without a noticeable change in yield.
2 No noticeable difference in yield has been found based on the complete dissolution of the suspension
3 Do not attempt to wash the initially acidic aq. layer, you will lose a significant amount of product for the obvious reasons.
4 DCM was tried, as well as EtOAc and CHCl3. CHCl3 gave best separation (no emulsion etc) but DCM was most practical