Allyl Alcohol → 3-(Quinolin-6-yl)propanal

HRID 1966368Notes

Reaction equation

HRID 1966368 reaction equation
O1CCOCC1.Br[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][CH:12]=[CH:11]2.[CH2:18]([OH:21])[CH:19]=[CH2:20].CN(C1CCCCC1)C1CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(OC)(C)(C)C>[N:14]1[C:15]2[C:10](=[CH:9][C:8]([CH2:20][CH2:19][CH:18]=[O:21])=[CH:17][CH:16]=2)[CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 7858Allyl AlcoholHCID 24210N-Methyl dicyclohexylamineHCID 312751,4-DioxaneHCID 792436-Bromoquinoline

Product 1

HCID 229313103-(Quinolin-6-yl)propanalYield 52.7%

Reagents, catalysts & solvents 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
55 °C

Procedure

A 22 L flask was charged with tris(dibenzylideneacetone)dipalladium(0) (70.0 g, 0.076 mol, 0.015 equiv), tri-tert-butylphosphonium tetrafluoroborate (44 g, 0.152 mol, 0.03 equiv), and dioxane (12 L) at room temperature. The resulting solution was then degassed with a steady stream of nitrogen for 20 min before 6-bromoquinoline (8, 1055 g, 5.07 mol, 1.0 equiv), allyl alcohol (588 g, 10.1 mol, 2.0 equiv), and N-methyl-N-cyclohexylcyclohexylamine (1186 g, 6.08 mol, 1.2 equiv) were added at room temperature. The resulting reaction mixture was stirred at 50- to 55° C. for 8-12 h. When TLC and LC/MS showed that the reaction was deemed complete, the reaction mixture was cooled to room temperature before methyl tert-butyl ether (MTBE, 10 L) was added to the reaction mixture. The resulting mixture was stirred at room temperature for 10 min before being filtered through a plug of celite. The filtrate was concentrated under the reduced pressure and the residue was purified by flash column chromatography (SiO2, 20-80% ethyl acetate in heptane gradient elution) to afford 3-(quinolin-6-yl)propanal (9, 495 g, 939.1 g theoretical, 52.7%) as a yellow oil, which solidified partially upon standing at 0-5° C. For 9: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.75 (t, 1H, J=1.24 Hz), 8.83 (dd, 1H, J=4.15 Hz, 1.66 Hz), 8.25 (dd, 1H, J=8.3, 1.03 Hz), 7.93 (d, 1H, J=8.71 Hz), 7.76 (d, 1H, J=1.45 Hz), 7.64 (dd, 1H, J=8.72 Hz, 2.08 Hz), 7.48 (dd, 1H, J=8.30 Hz, 4.36 Hz), 3.05 (t, 2H, J=7.26 Hz), 2.89 (t, 2H, J=7.26 Hz); C12H11NO (MW 185.22), LCMS (EI) m/e 186 (M++H).

Workup

  1. additionwere added at room temperature
  2. customThe resulting reaction mixture
  3. additionwas added to the reaction mixture
  4. stirringThe resulting mixture was stirred at room temperature for 10 min
  5. filtrationbefore being filtered through a plug of celite
  6. concentrationThe filtrate was concentrated under the reduced pressure
  7. customthe residue was purified by flash column chromatography (SiO2, 20-80% ethyl acetate in heptane gradient elution)

Sources & evidence

ORD record
ord-22ebe40b36f140cc995f719b254766e0
Source dataset
uspto-grants-2013_04
Patent number
US08420645B2

Reaction notes

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