One-pot synthesis of carbamates and thiocarbamates from Boc-protected amines

One‐Pot Synthesis of Thiocarbamates

“…Thiocarbamates are a well-established substance class within organic chemistry. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Their versatility is partially derived from their isomeric character: O-organyl and S-organyl thiocarbamates as well as dithiocarbamates are well known. Some are biologically active and hence they have found applications as antifertility agents, antivirals, pesticides and herbicides (e. g. the S-organyl thiocarbamates Thiobencarb, Orbencarb, and Molinate).…”

Efficient access to 3′-O-phosphoramidite derivatives of tRNA relatedN6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A)

“…In all cases, the nal condensation of isocyanate 2 with 3a was performed in the presence of Et 3 N (2-fold molar excess over the Tf 2 O activator used for isocyanate formation) in boiling toluene for 16 h. It was reported that addition of Et 3 N, which is an effective scavenger of triuoromethanesulfonic acid (generated in the step of isocyanate formation), helps to maintain a concentration of the unprotonated amine component sufficient for effective nucleophilic attack on the isocyanate moiety. 48,50 To optimize the triic anhydride (Tf 2 O) mediated conversion of N-Boc-protected threonine 1 (a dichloromethane solution) into the isocyanate derivative 2 (the rst step of the one-pot synthesis of 4a) we were changing the amount of Tf 2 O activator, basicity of amine, temperature and reaction time (entries 1-7). When the amount of 2 reached the plateau (TLC monitoring) the reaction mixture was concentrated, the residue was dissolved in toluene and Et 3 N and the nucleoside substrate 3a was added.…”

“…In so far reported procedures for the one-pot syntheses of ureas from carbamates, the use of an excess of amine substrate, usually up to 3 equivalents (or more for less nucleophilic amines) is recommended to obtain the higher efficiency of the process. 48,50,51 However, in the case of t 6 A/ms 2 t 6 A synthesis, the amine nucleoside substrate, especially non-native 2-methylthioadenosine (ms 2 A) is a very costly reagent. Therefore, in the second step of optimizations we examined an excess of N-Boc protected L-threonine derivative 1 to nucleoside 3a in a range 1.5-2.5 (entries 8-10), yet the concentrations of Tf 2 O and 2-Cl-Py against 1 were kept as determined previously (entry 2).…”

“…N-Boc protecting group). [44][45][46][47][48][49][50][51][52][53] Most likely, such variant of the isocyanate method (Scheme 1, path B3) applied in the synthesis of the 3 0 -O-phosphoramidite derivatives of t 6 A/ms 2 t 6 A would be greatly advantageous in comparison to our previous isocyanate route (Scheme 1, path B2) owing to a smaller number of synthesis steps in the preparation of threonine derivative (the removal of N-Boc protection is unnecessary) and escaping the use of toxic phosgene.…”

Synthesis of Urea Derivatives in Two Sequential Continuous-Flow Reactors

“…A subsequent study aiming for the synthesis of carbamates and thiocarbamates made similar observations regarding the base in the isocyanate formation step. 20 Unfortunately, this unusual specificity of the reaction remained unexplained. Rapid advances in flow chemical methods 21−26 made continuous processing suitable for the synthesis of APIs and their intermediates.…”