Acetic Acid → 2,3-Bis(((1,1-dimethylethyl)dimethylsilyl)oxymethyl)cyclobutanol

Temperatur

-78 °C

2,3-Bis(((1,1-dimethylethyl)dimethylsilyl)oxymethyl)cyclobutanone (10.2 g, 28.4 mmol) from Step B was dissolved in tetrahydrofuran (THF) and the solution was cooled to -78° C. under a nitrogen atmosphere. To the THF solution at -78° C. was slowly added, with stirring, 31 mL (31 mmol) of potassium tri-sec-butylborohydride (sold by Aldrich Chemical Company as a 1M solution in THF under the registered trademark K-Selectride®). After stirring for 0.5 h at -78° C., the reaction mixture was allowed to warm to 0° C. and it was stirred for 40 minutes at 0° C. One equivalent (1.9 mL) of glacial acetic acid was added and the reaction mixture was concentrated in vacuo to approximately 50 mL. The concentrate was diluted with 1 L of methylene chloride and the resultant solution was washed with 400 mL of 5% aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered and concentrated to a syrup. The syrup (15.5 g) was chromatographed on a 4.5×45 cm silica gel column eluted @ 2-5 psi with 2 L of methylene chloride. All fraction containing the desired product were combined and concentrated. The residue (10 g) was rechromatographed as described above to give 6.3 g (62% yield) of the title compound as a syrup; 1H NMR (CDCl3) δ 0.07 (d, 12H), 0.92 (d, 18H), 2.01 (m, 1H), 2.13 (m, 2H), 2.25 (m, 1H), 2.40 (m, 1H), 3.35 (d, 1H), 3.55 (m, 2H), 3.86 (dd, 1H), 3.98 (dd, 1H); MS DCI-NH3M/Z: 361 (M+H)+.

1. stirringAfter stirring for 0.5 h at -78° C.
2. temperatureto warm to 0° C.
3. stirringit was stirred for 40 minutes at 0° C
4. concentrationthe reaction mixture was concentrated in vacuo to approximately 50 mL
5. additionThe concentrate was diluted with 1 L of methylene chloride
6. washthe resultant solution was washed with 400 mL of 5% aqueous sodium bicarbonate solution
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated to a syrup
10. customThe syrup (15.5 g) was chromatographed on a 4.5×45 cm silica gel column
11. washeluted @ 2-5 psi with 2 L of methylene chloride
12. additionAll fraction containing the desired product
13. concentrationconcentrated
14. customThe residue (10 g) was rechromatographed

ORD-Eintrag

ord-a85057aaa6914c52a223e4b75364a097

Quelldatensatz

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05246931