Hydrochloric Acid → HCID 21018400, compound

Participants

Reaction Steps

To the THP protected alcohol (0.945 g, 4 mmol) in THF was added 4d.1 (1.311 g, 1.0 eq), followed by addition of Ph3P (1.311 g, 1.25 eq) and di-tert butyl azodicarboxylate (1.15 g, 1.25 eq). The mixture was stirred at room temperature overnight. The mixture was then concentrated and purified by flash column chromatography to give 5-bromo-1-[2,6-difluorobenzyl]-3-{3-(2-tetrahydro-2H-pyranyloxy)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione [MS (CI) m/z 464.9 & 466.9 (MH+-THP); tR=2.782 (method 4)]. 5-Bromo-1-[2,6-difluorobenzyl]-3-{3-(2-tetrahydro-2H-pyranyloxy)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione (110 mg) was treated with 1N HCl (10 mL)/MeOH (10 mL) at room temperature for 1 hour. The reaction mixture was concentrated and purified by prep TLC plate to yield 5-bromo-1-[2,6-difluorobenzyl]-3-{3-hydroxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione. MS (CI), m/z 464.9 & 466.9 (MH+); tR=2.613 (method 4). Suzuki coupling with 2-fluoro-3-methoxyphenylboronic acid by the procedure of Step 8B gave compound 8b.

Provenance & Evidence