Sodium hydride → Tert-butyl(+/-)-(1S,5R)-3-methylbicyclo[3.2.0]hept-3-en-6-ylideneacetate

4-Methyl-3-hydroxyhept-6-enoic acid (2.21 g, 13.9 mmol) was dissolved in acetic anhydride (14 mL). To the solution, potassium acetate (3.29 g, 33.4 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was heated to 110 to 120° C. and stirred for 3.5 hours. To the reaction solution, ice water and toluene were then added, and this mixture was stirred at room temperature for 1 hour. The mixture was separated into aqueous and organic layers by the addition of saturated saline and toluene. Then, the organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline in this order, then dried over anhydrous magnesium sulfate, and then filtered. This filtrate was added to a reaction solution prepared by adding sodium hydride (>63% oil, 533.3 mg, 14.0 mmol) to a tetrahydrofuran solution (20 mL) of tert-butyl dimethoxyphosphorylacetate (3.24 g, 14.5 mmol) under ice cooling, and the mixture was further stirred for 1.5 hours. The reaction solution was separated into aqueous and organic layers by the addition of a saturated aqueous solution of ammonium chloride and saturated saline. The aqueous layer was subjected to extraction with ethyl acetate. These organic layers were combined, then washed with saturated saline, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.21 g, 40%, E/Z mixture).

1. temperatureThe reaction solution was heated to 110 to 120° C.
2. stirringstirred for 3.5 hours
3. stirringthis mixture was stirred at room temperature for 1 hour
4. customThe mixture was separated into aqueous and organic layers
5. additionby the addition of saturated saline and toluene
6. washThen, the organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline in this order
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. additionThis filtrate was added to a reaction solution
10. customprepared
11. stirringthe mixture was further stirred for 1.5 hours
12. customThe reaction solution was separated into aqueous and organic layers
13. additionby the addition of a saturated aqueous solution of ammonium chloride and saturated saline
14. extractionThe aqueous layer was subjected to extraction with ethyl acetate
15. washwashed with saturated saline
16. dry with materialdried over anhydrous magnesium sulfate
17. distillationThe solvent was distilled off under reduced pressure
18. customthe residue was purified by silica gel column chromatography
19. customto obtain the compound of interest as a pale yellow oil substance (1.21 g, 40%, E/Z mixture)

ORD-Eintrag

ord-53e72118458f46128357a7ecf6debb8e

Quelldatensatz

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07947738B2