Ethanolamine → HCID 23141391, compound

HRID 558441Notes

Reaction equation

HRID 558441 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][C:3]=1/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH2:49]([CH2:51][NH2:52])[OH:50]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[OH:50][CH2:49][CH2:51][NH:52][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][C:3]=1/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 700EthanolamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23141402HCID 23141402, compound

Product 1

HCID 23141391HCID 23141391, compound

Reagents, catalysts & solvents 1

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalyst

Conditions

Temperature
65 °C

Procedure

The interior of a container containing 4-bromo-3-[(E)-2-(4-trifluoromethoxy-phenyl)-vinyl]-benzamide (50.2 mg) obtained in Example 2-5-1, 2.8 mg of tris(dibenzylideneacetone) dipalladium(0), 10 μL of ethanolamine, and 2.6 mg of 2-(dicyclohexylphosphino)biphenyl was purged with argon. A 1.0M tetrahydrofuran solution (1 mL) of lithium bis(trimethylsilyl)amide was added into the container, and the mixture was stirred for 3.5 hours at 65° C. Then, 2.0 mg of tris(dibenzylideneacetone) dipalladium(0), and 10 μL of ethanolamine were further added, the interior of the container was purged with argon, and the mixture was stirred for 13.5 hours at 65° C. The reaction mixture was cooled to room temperature, and 2 mL of 1N hydrochloric acid was added for neutralization, followed by extracting the aqueous layer with ethyl acetate 4 times. After the respective organic layers were combined, the combined organic layer was filtered through Presep Dehydration Column (produced by Wako Pure Chemical Industries), and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to 11 g silica gel column chromatography to obtain 5.6 mg of 4-(2-hydroxy-ethylamino)-3-[(E)-2-(4-trifluoromethoxy-phenyl)-vinyl]-benzamide with the use of an eluant (dichloromethane and methanol, 15:1).

Workup

  1. customwas purged with argon
  2. additionA 1.0M tetrahydrofuran solution (1 mL) of lithium bis(trimethylsilyl)amide was added into the container
  3. additionThen, 2.0 mg of tris(dibenzylideneacetone) dipalladium(0), and 10 μL of ethanolamine were further added
  4. customthe interior of the container was purged with argon
  5. stirringthe mixture was stirred for 13.5 hours at 65° C
  6. temperatureThe reaction mixture was cooled to room temperature
  7. addition2 mL of 1N hydrochloric acid was added for neutralization
  8. extractionby extracting the aqueous layer with ethyl acetate 4 times
  9. filtrationthe combined organic layer was filtered through Presep Dehydration Column (produced by Wako Pure Chemical Industries)
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f882c8d854546e0b9fe495a64e33ccf
Source dataset
uspto-grants-2011_11
Patent number
US08063046B2

Reaction notes

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