4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidinyl-5-yl-formyl

To a 100mL three-necked flask, add 50mL of tetrahydrofuran, 2.3g (60mmol) sodium borohydride, and 7.6g (20mmol) (HPLC: 99.7%) pyrimidinyl ester (II). Cool to -20℃, and slowly add 34.8g (120mmol) boron trifluoride tetrahydrofuran complex. Heat to 65℃ and maintain the reaction temperature for 24h. After the reaction is complete, cool to room temperature, and slowly add hydrochloric acid (v/v = 5%) to the reaction solution. Stir for 0.5h, and then add saturated N2O2.

Adjust the pH to 7-8 with aHCO3, extract with CH2Cl2 (20 mL × 2), separate the aqueous layer, dry the CH2Cl2 layer with anhydrous sodium sulfate, filter, and concentrate the filtrate to dryness under reduced pressure to obtain 6.78 g of light yellow solid pyrimidinol (III), yield 96.0%;

In a 100 mL three-necked flask, add 17.65 g (50 mmol) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonamide)pyrimidin-5-methanol, 0.187 g (1.2 mmol) of TEMPO, 0.606 g (1.5 mmol) of Fe(NO3)3·9H2O, and 15 mL of dichloromethane, introduce O2, stir at 20 °C for 24 h, and monitor with TLC. After the reaction was complete, 30 mL of water was added, and the mixture was allowed to stand to separate into layers. The layers were then extracted with dichloromethane (20 mL × 2), and the organic layers were combined. The organic solvent was removed by vacuum distillation to give 17.23 g of white solid 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidinyl-5-yl-formyl (IV), with a yield of 98.2%.

Rosuvastatin intermediate.