N,N-Dimethylaniline → Tert-butyl 4-((6-chloropyrimidin-4-yl)methyl)phenylcarbamate

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Reaction Steps

Triethylamine hydrochloride (0.93 g 6.60 mmol), N,N-dimethylaniline (0.8 mL, 6.60 mmol), and POCl3 (3.7 mL, 39.6 mmol, 6 equiv) are added sequentially to a solution of [4-(6-hydroxy-pyrimidin-4-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (2.0 g, 6.60 mmol) in CH3CN (16.5 mL), at rt and under an argon atmosphere. The resulting yellow solution is stirred at rt for 1 h and then added to a stirred mixture of H2O/ice (1/1, v/v; 80 mL, total volume). The product is extracted in CH2Cl2 (2×200 mL). The organic phase is washed with an aqueous saturated solution of Na2CO3 (70 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel (170 g) column chromatography (CH2Cl2/Et2O, 95/5, then 90/10) to afford the title compound: ES-MS: 320.1 [M+H]+; single peak at tR=8.76 min (System 2); Rf=0.13 (CH2Cl2/Et2O, 95/5).

Provenance & Evidence