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

4-Propyl-3-hydroxyhept-6-enoic acid (2.79 g, 15.0 mmol) was dissolved in acetic anhydride (13 mL). To the solution, potassium acetate (3.52 g, 36.0 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was heated to 120° C. and stirred for 3 hours. To the reaction solution, ice water and n-pentane were then added, and this mixture was stirred overnight at room temperature. Saturated saline was added thereto, and the mixture was separated into aqueous and organic layers by the addition of n-pentane. Then, the organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline in this order and dried over anhydrous magnesium sulfate, and the solvent was then distilled off under reduced pressure. The residue was dissolved in tetrahydrofuran (50 mL). The solution was added to a reaction solution prepared in advance by adding sodium hydride (>65% oil, 761.9 mg, 20 mmol) to a tetrahydrofuran solution (50 mL) of tert-butyl dimethoxyphosphorylacetate (4.48 g, 20 mmol) under ice cooling, and the mixture was further stirred for 1 hour. 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 (1.81 g, 49%, E/Z mixture).

1. temperatureThe reaction solution was heated to 120° C.
2. stirringstirred for 3 hours
3. stirringthis mixture was stirred overnight at room temperature
4. additionSaturated saline was added
5. customthe mixture was separated into aqueous and organic layers
6. additionby the addition of n-pentane
7. washThen, the organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline in this order
8. dry with materialdried over anhydrous magnesium sulfate
9. distillationthe solvent was then distilled off under reduced pressure
10. dissolutionThe residue was dissolved in tetrahydrofuran (50 mL)
11. additionThe solution was added to a reaction solution
12. customprepared in advance
13. stirringthe mixture was further stirred for 1 hour
14. customThe reaction solution was separated into aqueous and organic layers
15. additionby the addition of a saturated aqueous solution of ammonium chloride and saturated saline
16. extractionThe aqueous layer was subjected to extraction with ethyl acetate
17. washwashed with saturated saline
18. dry with materialdried over anhydrous magnesium sulfate
19. distillationThe solvent was distilled off under reduced pressure
20. customthe residue was purified by silica gel column chromatography
21. customto obtain the compound of interest as a pale yellow oil substance (1.81 g, 49%, E/Z mixture)

ORD record

ord-3b1a372986e24bf986b86a4e388d28a7

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07947738B2