Iodine → (2S,3R)-2-(N,N-Dibenzylamino)-3-tetradecanol

Temperature

60 °C

To a suspension of Mg (155 mg, 6.38 mmol) and a few crystals of I2 in THF (3.1 mL), an aliquot of 1-bromoundecane (0.25 mL, 1.12 mmol) was added and the mixture was stirred at 60° C. until the red color of the solution disappeared. Then the remainder of 1-bromoundecane (0.46 mL, 2.07 mmol) was added and the reaction was stirred at room temperature for 1 h. The Grignard solution formed thereof was cooled down to 0° C. and a solution of aldehyde 4 (323.5 mg, 1.28 mmol) in THF (1.6 mL) was added via cannula. After stirring overnight at room temperature, the reaction was quenched with HCl (3N, 10 mL) extracted with EtOAc (3×10 mL), washed successively with NaHCO3 (20 mL, sat. aq.) and brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography on silica (100% hexane to 10:1 hexane/EtOAc) to obtain a mixture of diastereoisomers. Further purification by HPLC on silica (95:5 to 80:20 hexane/MTBE) afforded pure anti alcohol 29 as a colorless oil (205 mg, 39% yield).

1. stirringthe reaction was stirred at room temperature for 1 h
2. customThe Grignard solution formed
3. temperaturethereof was cooled down to 0° C.
4. stirringAfter stirring overnight at room temperature
5. customthe reaction was quenched with HCl (3N, 10 mL)
6. extractionextracted with EtOAc (3×10 mL)
7. washwashed successively with NaHCO3 (20 mL, sat. aq.) and brine (20 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude was purified by column chromatography on silica (100% hexane to 10:1 hexane/EtOAc)
11. customto obtain
12. additiona mixture of diastereoisomers
13. customFurther purification by HPLC on silica (95:5 to 80:20 hexane/MTBE)

ORD record

ord-fbb3599bbaef4aa488aa47537434fcf5

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07138547B2