Tri-o-tolylphosphine → HCID 86706069, compound

HRID 2176231Notes

Reaction equation

HRID 2176231 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][O: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.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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][O:30][CH2:29][CH2:28][O:27]1)=[O:25]

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 4594378Bis(cyclohexylmethyl)amineHCID 86706059HCID 86706059, compoundHCID 86706068HCID 86706068, compound

Product 1

HCID 86706069HCID 86706069, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-carbamic acid tert-butyl ester (316 mg, 0.9 mmol), 2-vinyl-[1,4]dioxane-2-carboxylic acid methyl ester (154 mg, 0.9 mmol), palladium(II) acetate (41 mg, 0.18 mmol), tri(o-tolyl)phosphine (54 mg, 0.18 mmol) and N,N-dicyclohexylmethylamine (351 mg, 0.38 mL, 1.8 mmol) in acetonitrile (8 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 dichloromethane; brine and ice-cold 1 M hydrochloric acid were added to acidify the mixture to pH 2. The organic layer was separated and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 7:3 to 6:4 to afford the title compound (157 mg, 40%) as a yellow gum and as a 1:1 mixture of diastereoisomers. LCMS (m/z) 443.1 [M+H], Tr=2.34 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in dichloromethane
  4. additionbrine and ice-cold 1 M hydrochloric acid were added
  5. customThe organic layer was separated
  6. washwashed with brine
  7. filtrationThe organic solution was filtered through a hydrophobic frit
  8. customthe filtrate was evaporated
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-aa3eff3ae6f54c17a2dc9eaff929fbbd
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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