Tri-o-tolylphosphine → HCID 86706090, compound

HRID 2176251Notes

Reaction equation

HRID 2176251 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]([C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][C:14](Br)=[CH:15][CH:16]=2)[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24]([C:26]1([CH:32]=[CH2:33])[CH2:31][CH2:30][CH2:29][CH2:28][O:27]1)=[O:25].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(CNCC2CCCCC2)CCCCC1>C(#N)C.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]>[CH3:22][O:23][C:24]([C:26]1(/[CH:32]=[CH:33]/[C:14]2[CH:13]=[C:12]3[C:17]([CH:18]=[CH:19][C:10]([C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:21])[CH3:9])=[N:11]3)=[CH:16][CH:15]=2)[CH2:31][CH2:30][CH2:29][CH2:28][O:27]1)=[O:25]

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 4594378Bis(cyclohexylmethyl)amineHCID 86706059HCID 86706059, compoundHCID 86706088HCID 86706088, compound

Product 1

HCID 86706090HCID 86706090, compoundYield 32.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-carbamic acid tert-butyl ester (320 mg, 0.9 mmol), 2-vinyl-tetrahydro-pyran-2-carboxylic acid methyl ester (330 mg, 0.9 mmol), tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.09 mmol), tri(o-tolyl)phosphine (54 mg, 0.18 mmol) and N,N-dicyclohexylmethylamine (526 mg, 0.58 mL, 2.7 mmol) in acetonitrile (4 mL) was heated at 120° C. in a microwave reactor for 30 minutes. The reaction mixture was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate and the solution was washed with ice-cold hydrochloric acid (1 M). The aqueous layer was extracted with ethyl acetate and the organic extracts were combined and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated to afford 2-{(E)-2-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-vinyl}-tetrahydro-pyran-2-carboxylic acid methyl ester (130 mg, 21%) as an oil LCMS (m/z) 441.1 [M+H], Tr=2.75 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthe solution was washed with ice-cold hydrochloric acid (1 M)
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washwashed with brine
  7. filtrationThe organic solution was filtered through a hydrophobic frit
  8. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-bf88941acc2a4445b3619fa9ef83c2e8
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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