Enantiomeric separation and purification of 2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid amide derivatives

A method comprising:

• separating an S-enantiomer from an R-enantiomer, wherein said S-enantiomer and said R-enantiomer are provided in a racemic mixture and wherein each of said S-enantiomer and said R-enantiomer is a compound of Formula I:
• wherein:
• R1 is C1-4 alkylene-LG wherein LG is a leaving group;
• R2 is hydrogen, hydroxyl, halo, cyano, C1-3 alkyl, C1-3 alkoxy, C1-3 fluoroalkyl, or C1-3 fluoroalkoxy;
• R3 and R4 are independently C1-3 alkyl, C7-10 aralkyl, or R3 and R4, together with the nitrogen to which they are attached, form a nitrogen-containing C4-6 aliphatic ring optionally comprising 1 further heteroatom selected from nitrogen, oxygen and sulfur;
• Y1 is O, S, SO, SO2 or CH2;
• Y2 is CH2, CH2—CH2, CH(CH3)—CH2, CH2—CH2—CH2 or CH—(CH—CH2—CH—CH2)—CH;
• said variable bond is above the plane for the S-enantiomer and below the plane for the R-enantiomer as illustrated respectively in Formulas I-S and I-R:
• dissolving either one of said separated enantiomers in a suitable organic solvent to obtain a solution;
• precipitating said dissolved enantiomer out of the solution wherein said precipitating step comprises addition of water;
• and
• isolating the precipitate.