2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 1,1-Dimethylethyl benzoate

HRID 1645358Notes

Reaction equation

HRID 1645358 reaction equation
Cl.N1CC[C@H](OC2C=CC(NC(C3N(CC)C4C(C=3)=C(OCC)C=CC=4)=O)=CC=2)C1.[C:31]([O:35][C:36](=[O:44])[C:37]1[CH:42]=[CH:41][C:40](Br)=[CH:39][CH:38]=1)([CH3:34])([CH3:33])[CH3:32].C(C1C=C(C(C)C)C=C(C(C)C)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.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]>[C:31]([O:35][C:36](=[O:44])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 11334366Tert-butyl 4-bromobenzoateHCID 23676156Sodium t-butoxideHCID 66772950HCID 66772950, compound

Product 1

HCID 698861,1-Dimethylethyl benzoateYield 193.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

4-Ethoxy-1-ethyl-1H-indole-2-carboxylic acid [4-((S)-pyrrolidin-3-yloxy)-phenyl]-amide hydrochloride (103 mg, 0.24 mmol) was mixed with 4-bromo-benzoic acid tert-butyl ester (74 mg, 0.29 mmol) in dioxane (4 mL). To this solution was added tris(dibenzylideneacetone)dipalladium (Pd2(dba)3, 20 mg), (2′,4′,6′-triisopropyl-1,1′-biphenyl-2-yl)dicyclohexylphosphine (X-PHOS, 35 mg) and sodium tert-butoxide (70 mg, 0.72 mmol). The mixture was degassed with argon and then sealed. The stirred solution was heated at 105° C. for 2 hrs and solvents were evaporated. The residue was extracted with ethyl acetate and ammonium chloride solution. The organic layer was dried over sodium sulfate and then concentrated. The residue was purified through flash column chromatography using ethyl acetate in hexanes (5% to 60%) to give a white solid as 4-(S)-3-{4-[(4-ethoxy-1-ethyl-1H-indole-2-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (100 mg).

Workup

  1. customThe mixture was degassed with argon
  2. customsealed
  3. customsolvents were evaporated
  4. extractionThe residue was extracted with ethyl acetate and ammonium chloride solution
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified through flash column chromatography

Sources & evidence

ORD record
ord-24acc8076209468988f06c07c18cf7c2
Source dataset
uspto-grants-2012_02
Patent number
US08124766B2

Reaction notes

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