3-Phenylprop-2-Enal → HCID 118939037, compound

HRID 523118Notes

Reaction equation

HRID 523118 reaction equation
C1COCC1.[O:6]=[C:7]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH:19](=[O:28])[CH:20]=[CH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CC(O)C.CCCCCC>[O:28]=[C:19]1[O:6][C:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:20]1

Participants

5

Reactant 3

HCID 3073-Phenylprop-2-EnalHCID 8028TetrahydrofuranHCID 15349Ethyl benzoylformate

Product 1

HCID 118939037HCID 118939037, compound

Reagents, catalysts & solvents 1

HCID 21585144Isopropanol hexaneSolvent

Conditions

Temperature
23 °C

Procedure

A flame dried 2 dram vial equipped with a stirbar is brought into the glovebox and charged with (+)-4 (0.016 mmol, 0.10 equiv), TBD (6.6 mg, 0.048 mmol, 0.30 equiv), and 4 Å molecular sieves (100 mg). The vial is then sealed with a screw cap equipped with a teflon septa. The vial is then taken out of the glovebox and THF (0.80 mL), ethyl 2-oxo-2-phenylacetate (57 mg, 0.32 mmol, 2.0 equiv) and cinnamaldehyde (21 mg, 0.16 mmol) are added. The reaction mixture is then stirred at 23° C. for 36 hours (monitored by GC/MS). The crude reaction mixture is filtered through celite and an aliquot is taken to determine dr. After filtration the crude mixture is concentrated and the crude residue is purified by column chromatography on silca gel (2% EtOAc/Hex) to provide the pure products. Analytical data matches that reported in the literature (Li, Y. et al., Adv. Synth. Catal. 2008, 350, 1885, incorporated herein by reference). Major diastereomer (Cis) 1H NMR (500 MHz, CDCl3): δ 7.72-7.67 (m, 2H), 7.45-7.27 (m, 8H), 4.08 (dd, J=8.4, 4.1 Hz, 1H), 3.87-3.80 (m, 2H), 2.88 (dd, J=17.6, 8.4 Hz, 1H), 2.79 (dd, J=17.7, 4.1 Hz, 1H), 0.89 (d, J=7.7 Hz, 3H). Enantiomeric ratio is determined by chiral phase HPLC (chiralcel AD-H; i-PrOH-hexane, 2:98, 1.0 mL/min, 210 nm); tr (major)=39.4 min, tr (major)=60.0 min. and tr (minor)=17.1 min, tr (minor)=18.7 min. Absolute stereochemistry is assigned by analogy.

Workup

  1. customA flame dried 2 dram
  2. customvial equipped with a stirbar
  3. additioncharged with (+)-4 (0.016 mmol, 0.10 equiv), TBD (6.6 mg, 0.048 mmol, 0.30 equiv), and 4 Å molecular sieves (100 mg)
  4. customThe vial is then sealed with a screw
  5. customcap
  6. customequipped with a teflon septa
  7. additionare added
  8. customThe crude reaction mixture
  9. filtrationis filtered through celite
  10. filtrationAfter filtration the crude mixture
  11. concentrationis concentrated
  12. customthe crude residue is purified by column chromatography on silca gel (2% EtOAc/Hex)
  13. customto provide the pure products
  14. customtr (major)=39.4 min, tr (major)=60.0 min. and tr (minor)=17.1 min, tr (minor)=18.7 min

Sources & evidence

ORD record
ord-cb1c2f164edc44d9b84a3f2ffff00aee
Source dataset
uspto-grants-2016_05
Patent number
US09334297B2

Reaction notes

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