Triethylamine → Tert-butyl bicyclo[3.2.0]hept-3-en-6-ylideneacetate

Oxalyl chloride (10 mL) was added dropwise to a solution of (2E)-hepta-2,6-dienoic acid (3.27 g, 25.9 mmol) in toluene (60 mL) under ice cooling. The mixture was stirred for 20 minutes, then removed from the ice water bath, and gradually heated to room temperature. After stirring for 50 minutes, the reaction solution was stirred for 1 hour under heating to reflux. The solution was allowed to cool, and the solvent was then distilled off under reduced pressure. To the residue, toluene was further added, and the solvent was then distilled off again under reduced pressure. The residue was dissolved in toluene (20 mL), and this solution was added dropwise over 1 hour to a solution of triethylamine (9.19 g, 91 mmol) in toluene (20 mL) heated in advance to 90° C. After the completion of the dropwise addition, the mixture was further heated with stirring for 2 hours. The reaction solution was cooled, then diluted with saturated saline and water, and filtered through Celite. The filtrate was separated into organic and aqueous layers. The organic layer was then washed with 1 N hydrochloric acid, then dried over magnesium sulfate, and filtered. The filtrate was added to a reaction solution prepared in advance from a solution of tert-butyl dimethoxyphosphorylacetate (5.98 g, 25.9 mmol) in dimethoxyethane (20 mL) and sodium hydride (>65% oil, 986.7 mg, 25.9 mmol), and the mixture was stirred for 1.5 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride, saturated saline, and water were added in this order, and the reaction solution was subjected to extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. 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 (1.73 g, 32%, E/Z mixture).

1. customremoved from the ice water bath
2. stirringAfter stirring for 50 minutes
3. stirringthe reaction solution was stirred for 1 hour
4. temperatureunder heating to reflux
5. temperatureto cool
6. distillationthe solvent was then distilled off under reduced pressure
7. additionTo the residue, toluene was further added
8. distillationthe solvent was then distilled off again under reduced pressure
9. dissolutionThe residue was dissolved in toluene (20 mL)
10. temperatureheated in advance to 90° C
11. additionAfter the completion of the dropwise addition
12. temperaturethe mixture was further heated
13. stirringwith stirring for 2 hours
14. temperatureThe reaction solution was cooled
15. filtrationfiltered through Celite
16. customThe filtrate was separated into organic and aqueous layers
17. washThe organic layer was then washed with 1 N hydrochloric acid
18. dry with materialdried over magnesium sulfate
19. filtrationfiltered
20. additionThe filtrate was added to a reaction solution
21. stirringthe mixture was stirred for 1.5 hours
22. extractionthe reaction solution was subjected to extraction with ethyl acetate
23. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
24. filtrationfiltered
25. distillationThe solvent was distilled off under reduced pressure
26. customthe residue was purified by silica gel column chromatography
27. customto obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture)

ORD-Eintrag

ord-d2edc5768bb9453291284d7460233b60

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08324425B2