Lithium diisopropylamide → HCID 178459589, compound

Temperature

-78 °C

4-(1-tert-Butoxycarbonylamino-2-hydroxy-ethyl)-cyclohexanecarboxylic acid propyl ester (1-4) (4.26 g, 0.0129 mol, 1 eq) was dissolved in anhydrous THF (200 mL) under argon in a 1 L RB flask. The solution was cooled with an acetone-dry ice bath to −78° C. LDA (2.0 M solution) (51.7 mL, 0.103 mol, 8 eq) was added dropwise at −70° C. The reaction mixture was stirred at −70° C. for 2 hours. The reaction was quenched with MeOH (40 mL). The pH was adjusted to pH=4˜5 with 5% HCl. The mixture was extracted with Et2O (3×330 mL). The combined extracts were washed with brine (1×300 mL). After drying over Na2SO4 and filtration, the filtrate was concentrated under vacuum to dryness. The residue was purified on a silica gel column eluting with EtOAc/Hexanes 20˜40%) to give 3.78 g (88.7% yield) of the intermediate 1-5 as a mixture of cis- and trans-isomers. The 1H NMR (DMSO-d6) data is depicted in FIG. 4.

1. customThe reaction was quenched with MeOH (40 mL)
2. extractionThe mixture was extracted with Et2O (3×330 mL)
3. washThe combined extracts were washed with brine (1×300 mL)
4. dry with materialAfter drying over Na2SO4 and filtration
5. concentrationthe filtrate was concentrated under vacuum to dryness
6. customThe residue was purified on a silica gel column
7. washeluting with EtOAc/Hexanes 20˜40%)

ORD record

ord-946f479ca07544d39358ec9ab1e66d10

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785648B1