Sodium Iodide → 1-[3-(1,3-dioxolan-2-yl)propyl]-4-(5-Fluoro-2-pyrimidinyl) piperazine

Temperature

23 °C

A mixture of 4-(5-fluoro-2-pyrimidinyl)piperazine (7.29 g, 40.0 mmol), 2-(3-chloropropyl)-1,3-dioxolane (6.62 g, 5.8 mL, 44.0 mmol) and triethylamine (12.5 mL, 90.0 mmol) in 2-butanone (250 mL) was heated to reflux and treated dropwise (1h) with a solution of NaI (3.0 g, 20.0 mmol) in 2-butanone (70 mL). The reaction mixture was refluxed for 12 h then treated dropwise (1 h) with a solution of NaI (3.0 g, 20.0 mmol) in 2-butanone (70 mL) and refluxed for another 12 h. After cooling at 23° C., the solvent was evaporated in vacuo leaving a residue which was solubilized in EtoAC (400 mL). The organic solution was washed with aqueous NaOH solution (20 mL, 2N); the aqueous phase was extracted with EtoAC (2×50 mL). The organic extracts were combined, dried (MgSO4) and concentrated to dryness. The solution was chromatographed on a silica gel column (4.5×15 cm) using a mixture of 20% MeCN in EtoAc. Appropriate fractions were concentrated in vacuo leaving a pale yellow syrup which crystallized on standing, 10.5 g, mp 54°-55° C. (89%). Recrystallization from EtoAC-pet.ether mixture (1;14) gave an analytical sample, mp 55°-56° C.; 1HNMR (CDCl 3, 200 MHz) δ: 1.5-1.9 (m, 4H), 2.3-2.7 (m, 6H), 3.6-4.1 (m, 8H), 4.8-5.0 (m, 1H), 8.16 (s, 2H); IR (KBr) ν: 1610, 1555, 1489 cm-1 ; UV (EtOH) λ: 244 (ε 17239), 332 (ε 1948);

1. temperaturewas heated
2. temperatureto reflux
3. temperatureThe reaction mixture was refluxed for 12 h
4. temperaturerefluxed for another 12 h
5. customthe solvent was evaporated in vacuo
6. customleaving a residue which
7. washThe organic solution was washed with aqueous NaOH solution (20 mL, 2N)
8. extractionthe aqueous phase was extracted with EtoAC (2×50 mL)
9. dry with materialdried (MgSO4)
10. concentrationconcentrated to dryness
11. customThe solution was chromatographed on a silica gel column (4.5×15 cm)
12. additiona mixture of 20% MeCN in EtoAc
13. concentrationAppropriate fractions were concentrated in vacuo
14. customleaving a pale yellow syrup which
15. customcrystallized
16. customRecrystallization from EtoAC-pet
17. customether mixture (1;14) gave an analytical sample, mp 55°-56° C.

ORD record

ord-3a58838a44184dfeb65344f6c490a440

Source dataset

uspto-grants-1991_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04994460