Acetaldehyde → 1-(1-Hydroxy-ethyl)-3-triisopropylsilanyloxy-cyclopentanecarboxylic acid ethyl ester

Temperature

-78 °C

A cooled (−78° C.) solution of N,N-diisopropylamine (4.4 mL, 31.285 mmol) in anhydrous tetrahydrofuran (60 mL) was treated with n-butyllithium (2.5 M in hexanes, 11.7 mL, 29.329 mmol). After stirring at −78° C. for 30 min, the reaction mixture was treated with a solution of 3-triisopropylsilanyloxy-cyclopentanecarboxylic acid ethyl ester (6.15 g, 19.553 mmol) in anhydrous tetrahydrofuran (20 mL). After stirring at −78° C. for 40 min, the reaction mixture was treated with neat acetaldehyde (3.3 mL, 58.659 mmol). The cooling bath was removed and the reaction was stirred at room temperature for 50 min then quenched at 0° C. with a saturated solution of ammonium chloride (100 mL). The aqueous layer was extracted with dichloromethane (2×). The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 to afford the title compound (6.61 g, 94%) as a light yellow oil and as a complex mixture of diastereoisomers.

1. stirringAfter stirring at −78° C. for 40 min
2. customThe cooling bath was removed
3. stirringthe reaction was stirred at room temperature for 50 min
4. customthen quenched at 0° C. with a saturated solution of ammonium chloride (100 mL)
5. extractionThe aqueous layer was extracted with dichloromethane (2×)
6. filtrationfiltered through a phase separator
7. customthe volatiles were removed in vacuo
8. customThe residue was purified by silica gel chromatography
9. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1

ORD record

ord-a2ef01d1b0bf4b0f948869061a5e23bc

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062092B2