Hydrochloric Acid → HCID 59128275, compound

HRID 2426599Notes

Reaction equation

HRID 2426599 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:10]2[O:14]CCO2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH2:15]([NH2:17])[CH3:16].O(C(C)(C)C)[K].Cl>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:15]([NH:17][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[O:8][CH3:9])[CH:10]=[O:14])[CH3:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6341EthylamineHCID 179350472-(3-Bromo-4-methoxyphenyl)-1,3-dioxolaneHCID 178418922HCID 178418922, compound

Product 1

HCID 59128275HCID 59128275, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Through a solution of 2-(3-bromo-4-methoxy-phenyl)-[1,3]dioxolane (1.2 g, 4.63 mmol, 1.0 equiv; prepared as described in WO 01/74775 A1, Sanofi-Synthelabo) in toluene (6 mL) was bubbled ethylamine for 10 min. To this solution was added KOtert-Bu (0.67 g, 6.95 mmol, 1.5 equiv), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.029 g, 0.046 mmol, 0.01 equiv) and tris(dibenzylideneacetone)-dipalladium(0) (0.021 g, 0.023 mmol, 0.005 equiv) and the solution heated to 110° C. under microwave irradiation for 20 min. A few drops of a solution of 37% HCl were added and the reaction mixture heated again under microwave irradiation to 100° C. for 5 min. Evaporation of the solvent and purification of the crude reaction product by column chromatography on silica eluting with hexane/ethyl acetate (7:3) provided 0.52 g (63%) of the title compound. 1H NMR (300 MHz, CDCl3): δ1.24 (t, J=7.1 Hz, 3H), 3.16 (q, J=7.1 Hz, 2H), 3.86 (s, 3H), 4.17 (br s, 1H), 6.78 (d, J=8.1 Hz, 1H), 7.01 (d, J=1.9 Hz, 1H), 7.13 (dd, J=8.1 Hz, J=1.9 Hz, 1H), 9.75 (s, 1H). MS (ISP): 179.9 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated again under microwave irradiation to 100° C. for 5 min
  2. customEvaporation of the solvent and purification of the crude
  3. customreaction product by column chromatography on silica eluting with hexane/ethyl acetate (7:3)

Sources & evidence

ORD record
ord-c7dc8dbf010548c0ac5ff6b7a44ff9c1
Source dataset
uspto-grants-2011_06
Patent number
US07968568B2

Reaction notes

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