Dichloromethane → methyl 4-[2-(4'-nitro-1,1'-biphenyl-4-yl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate

HRID 9536

Reaction equation

HRID 9536 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:20])[CH2:9][C:10]2([C:16]([O:18][CH3:19])=[O:17])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[N+:21]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)([O-:23])=[O:22].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.O1CCOCC1.C1(C)C=CC=CC=1>[N+:21]([C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:20])[CH2:9][C:10]3([C:16]([O:18][CH3:19])=[O:17])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[CH:4][CH:3]=2)=[CH:26][CH:25]=1)([O-:23])=[O:22]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27735524-Nitrophenylboronic acidHCID 21985831Methyl 4-[2-(4-bromophenyl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate

Product 1

HCID 21985756methyl 4-[2-(4'-nitro-1,1'-biphenyl-4-yl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylateYield 79.3%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl 4-[2-(4-bromophenyl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate (820 mg, 2.40 mmol) and 4-nitrophenyl boronic acid (481 mg, 2.88 mmol) were combined in a dry flask under argon. Toluene (20 mL) and dioxane (5 mL) were added, and the resulting solution was degassed for 30 minutes by a flow of argon. The degassing was continued during the addition of saturated aqueous sodium carbonate (6 mL) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (98 mg, 0.12 mmol). The resulting mixture was then heated at 85° C. for 16 h before it was cooled to rt. Water was added, and the aqueous layer was extracted twice with ethyl acetate. The combined organic phases were then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (Biotage Flash 40) using 1:1 ethyl acetate/hexane to afford methyl 4-[2-(4′-nitro-1,1′-biphenyl-4-yl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate (730 mg, 79%). LC-MS ret. time 3.03; m/z 383.9 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.65–1.73 (m, 2H), 2.17–2.21 (m, 2H), 3.37 (s, 2H), 3.68 (s, 3H), 3.71–3.78 (m, 4H), 7.70 (d, 2H), 7.77 (d, 2H), 8.02 (d, 2H), 8.31 (d, 2H).

Workup

  1. customthe resulting solution was degassed for 30 minutes by a flow of argon
  2. temperaturewas cooled to rt
  3. extractionthe aqueous layer was extracted twice with ethyl acetate
  4. dry with materialThe combined organic phases were then dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by flash chromatography (Biotage Flash 40)

Sources & evidence

ORD record
ord-95ac54c9a77a48bb970bfef33b2bcba5
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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