A method of synthesising 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione wherein said method comprises: (a) preparing a compound of Formula: or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein: R is -CH(C 1 -C 6 alkyl)Ar or hydrogen; R 1 is CH 3; R 2 is H; R 3 is H; R 4 is -OCH 3; R 5 is -OCH 2 CH 3; R 6 is H; and Ar is aryl, wherein the compound of Formula is prepared by a process that comprises: (i) coupling an optionally substituted benzonitrile with a dialkylsulfone; (ii) hydrolysing the coupled product to afford a beta-ketosulfone; (iii) reacting the beta-ketosulfone with a chiral auxiliary to form a chiral enamine; (iv) reducing the chiral enamine to afford an N-protected aminosulfone; and (v) optionally deprotecting the N-protected aminosulfone; or (b) preparing a compound of Formula: or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein: R 1 is CH 3; R 2 is H; R 3 is H; R 4 is -OCH 3; R 5 is -OCH 2 CH 3; and R 6 is H, wherein the compound of Formula is prepared by a process that comprises: (i) condensing a chiral auxiliary with an aldehyde or ketone; adding a nucleophile to the condensed product; and deprotecting the addition product; or (ii) synthetic transformations selected from the group consisting of: addition of a chiral auxiliary to a styryl sulfone, enzymatic transamination, diastereoselective borohydride reduction of an Ellman adduct, stereoselective addition of aryl anion to aldimine with chiral auxiliary, asymmetric epoxidation and ring-opening with a sulfur nucleophile, and combinations thereof. (a) preparing a compound of Formula: or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein: R is -CH(C 1 -C 6 alkyl)Ar or hydrogen; R 1 is CH 3; R 2 is H; R 3 is H; R 4 is -OCH 3; R 5 is -OCH 2 CH 3; R 6 is H; and Ar is aryl, wherein the compound of Formula is prepared by a process that comprises: (i) coupling an optionally substituted benzonitrile with a dialkylsulfone; (ii) hydrolysing the coupled product to afford a beta-ketosulfone; (iii) reacting the beta-ketosulfone with a chiral auxiliary to form a chiral enamine; (iv) reducing the chiral enamine to afford an N-protected aminosulfone; and (v) optionally deprotecting the N-protected aminosulfone; or R is -CH(C 1 -C 6 alkyl)Ar or hydrogen; R 1 is CH 3; R 2 is H; R 3 is H; R 4 is -OCH 3; R 5 is -OCH 2 CH 3; R 6 is H; and Ar is aryl, wherein the compound of Formula is prepared by a process that comprises: (i) coupling an optionally substituted benzonitrile with a dialkylsulfone; (ii) hydrolysing the coupled product to afford a beta-ketosulfone; (iii) reacting the beta-ketosulfone with a chiral auxiliary to form a chiral enamine; (iv) reducing the chiral enamine to afford an N-protected aminosulfone; and (v) optionally deprotecting the N-protected aminosulfone; or (i) coupling an optionally substituted benzonitrile with a dialkylsulfone; (ii) hydrolysing the coupled product to afford a beta-ketosulfone; (iii) reacting the beta-ketosulfone with a chiral auxiliary to form a chiral enamine; (iv) reducing the chiral enamine to afford an N-protected aminosulfone; and (v) optionally deprotecting the N-protected aminosulfone; or (b) preparing a compound of Formula: or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein: R 1 is CH 3; R 2 is H; R 3 is H; R 4 is -OCH 3; R 5 is -OCH 2 CH 3; and R 6 is H, wherein the compound of Formula is prepared by a process that comprises: (i) condensing a chiral auxiliary with an aldehyde or ketone; adding a nucleophile to the condensed product; and deprotecting the addition product; or (ii) synthetic transformations selected from the group consisting of: addition of a chiral auxiliary to a styryl sulfone, enzymatic transamination, diastereoselective borohydride reduction of an Ellman adduct, stereoselective addition of aryl anion to aldimine with chiral auxiliary, asymmetric epoxidation and ring-opening with a sulfur nucleophile, and combinations thereof. R 1 is CH 3; R 2 is H; R 3 is H; R 4 is -OCH 3; R 5 is -OCH 2 CH 3; and R 6 is H, wherein the compound of Formula is prepared by a process that comprises: (i) condensing a chiral auxiliary with an aldehyde or ketone; adding a nucleophile to the condensed product; and deprotecting the addition product; or (ii) synthetic transformations selected from the group consisting of: addition of a chiral auxiliary to a styryl sulfone, enzymatic transamination, diastereoselective borohydride reduction of an Ellman adduct, stereoselective addition of aryl anion to aldimine with chiral auxiliary, asymmetric epoxidation and ring-opening with a sulfur nucleophile, and combinations thereof. (i) condensing a chiral auxiliary with an aldehyde or ketone; adding a nucleophile to the condensed product; and deprotecting the addition product; or (ii) synthetic transformations selected from the group consisting of: addition of a chiral auxiliary to a styryl sulfone, enzymatic transamination, diastereoselective borohydride reduction of an Ellman adduct, stereoselective addition of aryl anion to aldimine with chiral auxiliary, asymmetric epoxidation and ring-opening with a sulfur nucleophile, and combinations thereof.