3-Phenylprop-2-Enal → (S)-3-(4-Dimethylamino-2-methoxy-phenyl)-3-phenyl-propanol

Temperatur

0 °C

To a 50-mL roundbottom flask equipped with a magnetic stir bar was added (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidin-4-one (0.394 g, 1.60 mmol, 0.100 equiv), CH2Cl2 (16.0 mL), HCl (as a 4N solution in 1,4-dioxane, 0.400 mL, 1.60 mmol, 0.100 equiv), and N,N-dimethyl-m-anisidine (4.69 mL, 32.0 mmol, 2.00 equiv). The reaction vessel was cooled to 0° C. before the addition of cinnamaldehyde (2.06 ml, 16.0 mmol, 1.00 equiv). The solution was stirred for 12 h at 0° C. and then warmed to ambient temperature and stirred for an additional 6 h. At that time, the reaction mixture was added drop-wise to a stirring suspension of NaBH4 (0.750 g, 0.198 mmol, 1.24 equiv) in ethanol. After 5 min, the reduction was quenched with saturated aqueous NaHCO3 solution and diluted with CH2Cl2. The layers were separated and the organic was washed with saturated aqueous NaHCO3 and brine solutions. The resulting solution was dried over sodium sulfate and concentrated in vacuo to give a pale yellow residue, which was purified by silica gel chromatography. Gradient elution with 25–50% EtOAc in hexanes afforded the product as a colorless oil in 81% yield (3.70 g, 13.0 mmol); 74% ee. 1H NMR (300 MHz, CDCl3) δ 7.32–7.12 (m, 5H, ArH), 6.99 (d, J=8.2 Hz, 1H, ArH), 6.31 (dd, J=2.7, 8.8 Hz, 1H, ArH), 6.27 (d, J=2.2, Hz, 1H, ArH), 4.51 (dd, J=6.6, 8.8 Hz, 1H, ArCH), 3.83 (s, 3H, OCH3), 3.65–3.48 (m, 2H, CH2OH), 2.93 (s, 6H, N(CH3)2), 2.38–2.12 (m, 2H, CHCH2), 1.98 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3) δ 157.8, 150.5, 145.5, 128.8, 128.4, 128.2, 125.9, 121.3, 105.5, 96.6, 61.6, 55.9, 41.1, 38.7, 38.2.

1. customTo a 50-mL roundbottom flask equipped with a magnetic stir bar
2. temperaturewarmed to ambient temperature
3. stirringstirred for an additional 6 h
4. additionAt that time, the reaction mixture was added drop-wise
5. waitAfter 5 min
6. customthe reduction was quenched with saturated aqueous NaHCO3 solution
7. additiondiluted with CH2Cl2
8. customThe layers were separated
9. washthe organic was washed with saturated aqueous NaHCO3 and brine solutions
10. dry with materialThe resulting solution was dried over sodium sulfate
11. concentrationconcentrated in vacuo
12. customto give a pale yellow residue, which
13. customwas purified by silica gel chromatography
14. washGradient elution with 25–50% EtOAc in hexanes

ORD-Eintrag

ord-eda96803f0d64f57b54db25a83e52b4f

Quelldatensatz

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07173139B2