2-Methyl-3-butyn-2-ol → 1-(3-Chloro-4-methoxyphenyl)-4-methylpent-2-yne-1,4-diol

Temperature

-78 °C

To a −78° C. stirred solution of 2-methylbut-3-yn-2-ol (0.89 g, 10.710 mmol) in dry THF (50 mL), n-BuLi (16.0 mL, 27.001 mmol, 1.6 M in hexane) was added dropwise over 5 minutes under an inert atmosphere. The reaction mixture was stirred for 30 min at −78° C., and then a solution of 3-chloro-4-methoxybenzaldehyde (1.8 g, 10.710 mmol) in dry THF (10 mL) was added and stirring was continued for an additional 3 h at RT. The reaction mixture was then quenched with a saturated NH4Cl solution and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 2-4% EtOAc in hexanes to afford 1-(3-chloro-4-methoxyphenyl)-4-methylpent-2-yne-1,4-diol (0.69 g, 26%) as a yellow syrup.

1. additionwas added dropwise over 5 minutes under an inert atmosphere
2. stirringstirring
3. waitwas continued for an additional 3 h at RT
4. customThe reaction mixture was then quenched with a saturated NH4Cl solution
5. extractionextracted with EtOAc (2×50 mL)
6. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto obtain the crude product
11. customThe crude material was purified via silica gel column chromatography
12. washeluting with 2-4% EtOAc in hexanes

ORD record

ord-cc6b47e2d03d4affab86ac78e326eaae

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933074B2