Hydrochloric Acid → Methyl 4-methyl-3-hydroxyhept-6-enoate

Sodium hydride (>63% oil, 1.64 g, 43.1 mmol) was added to a solution of methyl 3-oxopentanoate (5.10 g, 39.2 mmol) in tetrahydrofuran (50 mL) under ice cooling, and the mixture was stirred in this state for 10 minutes. To the reaction solution, n-butyllithium (1.66 M solution in hexane, 25.9 mL, 43.1 mmol) was added dropwise, and the mixture was further stirred for 10 minutes under ice cooling. Then, allyl bromide (5.18 g, 43.1 mmol) was added thereto, and the mixture was stirred in this state for 30 minutes and then further stirred overnight at room temperature. To the reaction solution, 1 N hydrochloric acid and saturated saline were added, followed by extraction with diethyl ether. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in methanol (100 mL). To the solution, sodium borohydride (1.89 g, 50 mmol) was added under ice cooling, and the mixture was stirred in this state for 1.5 hours. 2 N hydrochloric acid (50 mL) was added thereto, and the mixture was stirred for 30 minutes. Then, saturated saline was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (5.72 g, 85%, mixture of diastereomers).

1. stirringthe mixture was further stirred for 10 minutes under ice cooling
2. stirringthe mixture was stirred in this state for 30 minutes
3. customfurther stirred overnight
4. customat room temperature
5. extractionfollowed by extraction with diethyl ether
6. washThe organic layer was washed with saturated saline
7. dry with materialdried over anhydrous magnesium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. dissolutionThe obtained residue was dissolved in methanol (100 mL)
10. stirringthe mixture was stirred in this state for 1.5 hours
11. stirringthe mixture was stirred for 30 minutes
12. additionThen, saturated saline was added
13. extractionfollowed by extraction with ethyl acetate
14. washThe organic layer was washed with saturated saline
15. dry with materialdried over anhydrous magnesium sulfate
16. distillationthe solvent was distilled off under reduced pressure
17. customThe residue was purified by silica gel column chromatography
18. customto obtain the compound of interest
19. additionas a pale yellow oil substance (5.72 g, 85%, mixture of diastereomers)

ORD record

ord-9e1f6f9356da4be28a3db9ccb77cfd10

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324425B2