| 92% |
With zinc dibromide; |
EXAMPLE 1 Preparation of 5-bromo-1-pentanyl acetate A 2 L three-neck, round-bottom flask equipped with a mechanical stirrer, a condenser and a nitrogen bubbler, was charged with 430.7 g (5.00 moles) of tetrahydropyran, 399.6 g (3.25 moles) of acetyl bromide, and 1.13 g of zinc bromide. The mixture was stirred under nitrogen at reflux for 2.5 hours, cooled to room temperature (ice bath), and transferred to a separatory funnel with 1 L of hexanes. The solution was washed with 250 mL of saturated aqueous sodium bicarbonate, 2*500 mL=1 L of deionized water, 500 mL of saturated brine, dried (anhydrous sodium sulfate) and filtered. The solvent was removed at 40/70 mm to give 692 g of crude 5-bromo-1-pentanyl acetate as a dark liquid. Distillation using a 32 cm Goodloe column gave 625.6 g (92% yield) of 5-bromo-1-pentanyl acetate as a colorless liquid, bp 60-67/0.08 mm. Calcd for C7 H13 BrO2: C 40.21; H, 6.27; Br, 38.22. Found: C, 39.72; H, 6.35; Br, 38.45. |
| 90% |
|
5-Bromopentanol-1-acetate (Compound XXXII) The procedure of U.S. Pat. No. 2,922,788 was used. Acetyl bromide (420 g, 3.4 mole) was combined with zinc (30 mesh, 3 g, 0.045 mole) and warmed to about 60 C. for 30 min with constant stirring. Tetrahydropyran (275 g, 3.2 mole) was added dropwise over 2 h. The reaction was cooled periodically during the addition period to keep the temperature between 60 and 70 C. The temperature was raised to 90 C. for 30 min, cooled, and then diluted with CH2 Cl2 (500 mL). Ice was added (200 g) and the reaction was shaken vigorously for several minutes The organic layer was washed (2*200 mL sat. NaHCO3; 200 mL brine), dried (MgSO4), and stripped of solvent in vacuum. Fractional distillation gave a nearly colorless oil (602.2 g, 90%): bp 120-1 C. (19 mm) (lit.121 109-11 C. (14 mm)); IR (film) cm-1 2950, 2900, 2870, 1740, 1465, 1460, 1435, 1395, 1370, 1245 (broad), 1045, 735; 1 H NMR (200 MHz, CDCl3) delta 4.08 (t, 6.3 Hz, 2H), 3.42 (t, 6.7 Hz, 2H), 2.06 (s, 3H), 1.09 (pentet, 7 Hz, 2H), 1.4-1.77 (m, 4H); 13 C NMR (22.5 MHz, CDCl3) delta 170.9, 64.0, 33.4, 32.3, 27.8, 24.6, 20.9; mass spectrum (70 eV) m/e 210, 208 (M+, not observed), 150, 148 (M+ - HOAc, 14.5, 14.9), 73 (8.0) 69 (66.0), 68 (13.9), 67 (6.1), 61 (23.6), 55 (9.6), 43 (100.0); high resolution mass spectrum (70 eV) m/e 149.9868, 147.9888 (calculated 149.9868, 147.9888 for C5 H9 Br). |
| 86% |
|
Zn dust (120 mg, cat. amount) was added to a stirred pure acetyl bromide (11.4 mL, 18.9 g, 136 mmol) under argon atmosphere. The reaction mixture was heated to 60 C and stirred for 15 minutes. Then the oil bath was removed and tetrahydropyrane (11.0 g, 128 mmol) was added dropwise to keep temperature in 60-70 C interval (addition rate ~1 drop in 2-3 seconds). After addition of whole amount of THP, that took about 1 hour, the reaction mixture was heated to 90 C, stirred for 30 minutes at this temperature and allowed to cool to room temperature. Reaction mixture was diluted with CH2Cl2 (40 mL) and poured into mixture of water with ice (~40mL). Organic layer was separated out and washed with saturated NaHCO3 solution (40 mL), brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The residue was distilled at the reduced pressure to give pure 5-bromopentyl acetate (22.9 g, 110 mmol, 86%) with bp = 103 C/7 torr. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
