Citric Acid → (S)-5-Phenyl-1-(trimethylsilyl)pent-1-yn-3-ol

Temperature

0 °C

Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); n-butyllithium (2.5 M in hexanes, 474 μL, 1.18 mmol, 3 eq.) was added dropwise to a solution of (S)-5-phenylpent-1-yn-3-ol 86 (63.3 mg, 0.39 mmol, 1 eq.) in THF (1 ml) at −78° C. The mixture was allowed to warm to 0° C. and stirred 30 min before being cooled to −78° C. TMSCl (148.2 μL, 1.18 mmol, 3 eq.) was added dropwise and the mixture was allowed to warm to r.t. and stirred for 2 h. Citric acid (65 mg) in methanol (0.7 ml) was added and the mixture stirred for 1 h. The mixture was poured into a mixture of brine (3 ml) and Et2O (5 ml). The aqueous layer was extracted with Et2O (3×10 ml) and the combined organic phases were washed with brine (10 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (9:1), giving the title product 87 as a clear, colourless oil (18.5 mg, 15.5%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)).

1. temperaturebefore being cooled to −78° C
2. temperatureto warm to r.t.
3. stirringstirred for 2 h
4. stirringthe mixture stirred for 1 h
5. extractionThe aqueous layer was extracted with Et2O (3×10 ml)
6. washthe combined organic phases were washed with brine (10 ml)
7. dry with materialbefore being dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto give the crude product
11. customThis was purified by column chromatography on silica
12. washeluting with petrol/Et2O (9:1)

ORD record

ord-8f212250e61449d8ab2e58b8f284712b

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242954B2