I[CH2:2][C:3]([OH:5])=[O:4].[CH3:6][O:7][CH2:8][C:9]1[S:13][C:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:11][N:10]=1.[H-].[Na+]>O1CCCC1>[C:17]([O:16][C:15]([N:14]=[C:12]1[N:11]([CH2:2][C:3]([OH:5])=[O:4])[N:10]=[C:9]([CH2:8][O:7][CH3:6])[S:13]1)=[O:21])([CH3:20])([CH3:19])[CH3:18]Iodoacetic acid (409.3 g, 2.2 mol, 1.5 eq) is added in one portion to a solution of tert-butyl [5-(methoxymethyl)-1,3,4-thiadiazol-2-yl]carbamate a31 (360 g, 1.468 mol, 1 eq) in tetrahydrofurane (3 l) at room temperature. Sodium hydride (52.83 g, 2.2 mol, 1.5 eq) is then added portionwise, in 30 minutes, at room temperature. The reaction mixture is heated at 60° C. for the night, and the solvent is evaporated under reduced pressure. Water is added to the residue, the solution is acidified to pH=2 with aqueous 6N HCl, then extracted with CH2Cl2. The organic layer is washed with 10% aqueous Na2S2O3 (to remove the coloration of iodine) and evaporated to dryness to furnish 455.7 g of {2-[(tert-butoxycarbonyl)imino]-5-(methoxymethyl)-1,3,4-thiadiazol-3(2H)-yl}acetic acid a33 which is used directly in the next step without any further purification.
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