Diisopropylamine → 3-Cyclohexyl-3-hydroxy-1-(2-iodophenyl)propan-1-one

Temperature

-30 °C

To a solution of diisopropylamine (1.6 mL, 11.1 mmol) in THF (38 mL) at 0° C. was added n-BuLi (4.1 mL, 10.2 mmol) under an atmosphere of N2. After 30 min the solution was cooled to −30° C. and a solution of 1-(2-iodophenyl)ethanone (2.27 g, 9.23 mmol) in THF (6 mL) was added dropwise to the mixture and was stirred for 45 min at −30° C. The mixture was cooled to −78° C. and cyclohexylcarboxaldehyde (1.2 mL, 9.69 mmol) was added dropwise and the mixture was allowed to warm to −40° C. over 2 h. The reaction was quenched by the addition of saturated aqueous NH4Cl. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash column chromatography to afford the title compound as yellow oil (2.56 g, 78%). 1H NMR: 1.02-1.27 (m, 4H), 1.41-1.49 (m, 1H), 1.66-1.76 (m, 4H), 1.89 (d, 1H, J=12.4 Hz), 2.88 (d, 1H, J=3.2 Hz), 2.98 (dd, 1H, J=9.2 Hz, 17.2 Hz), 3.13 (dd, 1H, J=2.0 Hz, 17.2 Hz), 3.99-4.01 (m, 1H), 7.11-7.15 (m, 1H), 7.42 (d, 2H, J=4.4 Hz), 7.93 (d, 1H, J=8.0 Hz).

1. temperatureThe mixture was cooled to −78° C.
2. temperatureto warm to −40° C. over 2 h
3. customThe reaction was quenched by the addition of saturated aqueous NH4Cl
4. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by flash column chromatography

ORD record

ord-a87de9525a3f4f3e85bde70c3a89dbeb

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388191B2