1,2-Dibromoethane → (2R)-5-hexyl-4-hydroxy-2-undecyl-2,3-dihydropyran-6-one

Temperature

80 °C

To a 1-L, 3-necked, round-bottomed flask fitted with a Claisen adapter with N2 inlet, a West condenser and a thermocouple-J-KEM controller and a rubber septum was added 13.9 g (0.572 g-atom, 3.2 equiv.) of magnesium (from Chromasco) was added. A small flake of 12 (about 45 mg) was added and the mixture was heated to about 80° C. 1,2-Dibromoethane (3.4 g, 18 mmol) and 350 mL of THF were added to the hot Mg/I2 mixture to activate the metal surface. Methyl (3R)-3-[(2-bromo-1-oxooctyl)oxy]-tetradecanoate (82.9 g, 179 mmol) from Example 2,1,2-dibromoethane (33.6 g, 179 mmol) and 400 mL of THF were added to the addition funnel. This mixture was slowly added to the Mg/THF mixture at reflux over about 1 h. The reaction mixture was stirred overnight (14 h) at about 60° C. The resulting yellow solution was decanted away from the metal into a 1-L, round-bottomed flask. The residual Mg metal was rinsed twice with 60 mL of THF. The combined THF solution was concentrated on a rotary evaporator. The syrupy mixture was taken up in 1750 mL of methylene chloride and added to a mixture of 500 mL of water, 200 mL of ice and 98 mL of 10% HCl in a separatory funnel. The aqueous layer was removed, the organic layer washed once with 200 mL of saturated sodium chloride, dried (NaSO4), filtered, and the solvent removed on a rotary evaporator. The crude white solid (66.7 g) was slurried in 100 mL of hexane, cooled to 0° C., filtered, and rinsed twice with 50 mL of cold hexane. The isolated white solid was dried in an oven at 40° C. under reduced pressure (10 mm Hg) overnight resulting in 28.4 g of (6R)-3-hexyl-4-hydroxy-6-undecyl-5,6-dihydropyran-2-one (45-50% yield based on methyl (R)-3-hydroxytetradecanoate).

1. additionwas added
2. temperatureat reflux over about 1 h
3. customThe resulting yellow solution was decanted away from the metal into a 1-L, round-bottomed flask
4. washThe residual Mg metal was rinsed twice with 60 mL of THF
5. concentrationThe combined THF solution was concentrated on a rotary evaporator
6. additionadded to a mixture of 500 mL of water, 200 mL of ice and 98 mL of 10% HCl in a separatory funnel
7. customThe aqueous layer was removed
8. washthe organic layer washed once with 200 mL of saturated sodium chloride
9. dry with materialdried (NaSO4)
10. filtrationfiltered
11. customthe solvent removed on a rotary evaporator
12. temperaturecooled to 0° C.
13. filtrationfiltered
14. washrinsed twice with 50 mL of cold hexane
15. customThe isolated white solid was dried in an oven at 40° C. under reduced pressure (10 mm Hg) overnight

ORD record

ord-0b266d0c47ff4a80b641b59edbc1756a

Source dataset

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06858749B2