Acetic Anhydride → 4-[1-[1-[Bis(4-fluorophenyl)methyl]piperazin-4-yl]-2-acetoxy-3-propanylthio]pyridine

Temperature

60 °C

To 4-mercaptopyridine (0.555 g, 5 mmol) in DMF (5 mL) with triethylamine (0.7 mL, 5 mmol) was added 1-(1-chloro-2-hydroxy-3-propanyl)-4-(4, 4'-difluorobenzhydryl) piperazine (1.91 g, 5 mmol) in DMF (15 mL) dropwise over 15 minutes under nitrogen. After 8 days, the reaction mixture was heated to 60° C. and stirred for 3 days. The DMF was removed in vacuo (1 mmHg, 60° C.) and to this crude material was added methylene chloride (5 mL), acetic anhydride (5 mmol, 0.47 mL) and triethylamine (5 mmol, 0.7 mL), and the mixture was stirred overnight. Silica gel flash chromatography using 10% methanol:methylene chloride gave an amber oil which was dissolved in methylene chloride (10 mL) and extracted with saturated sodium bicarbonate (2×20 mL), water (1×20 mL), saturated brine (1×20 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give pure product (0.38 g, 15.3%); DCI/MS (M+1)= 498; 300 MHz 1H NMR (CDCl3)δ: 8.4(d,2H,J=1.25 Hz), 7.3 (m,4H), 7.2 (d,2H,J=1.4 Hz), 6.95 (m, 4H), 5.1 (m, 1H), 4.2 (s, 1H), 3.3 and 3.2 (d of d and d of d, 2H), 2.6 (d, 2H,J=6.1 Hz), 2.35 (m, 8H), 2.0 (s,3H).

1. customThe DMF was removed in vacuo (1 mmHg, 60° C.) and to this crude material
2. stirringthe mixture was stirred overnight
3. extractionextracted with saturated sodium bicarbonate (2×20 mL), water (1×20 mL), saturated brine (1×20 mL)
4. dry with materialdried over sodium sulfate
5. customThe solvent was removed in vacuo

ORD record

ord-8bf179eeca7a4f2fadb4200bd644a342

Source dataset

uspto-grants-1993_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05215987