Water → HCID 69357176, compound

HRID 852537Notes

Reaction equation

HRID 852537 reaction equation
C(OC(=O)[C:7]1[CH:12]=[C:11]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[CH:10]=[C:9](Br)[CH:8]=1)(C)(C)C.C[C:22](C)([O-:24])C.[Na+].C1(P(C2CCCCC2)[C:34]2C=CC=[CH:36][C:35]=2[C:40]2C=CC=CC=2)CCCCC1.[CH2:52]([NH:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[CH3:53].[OH2:62]>CCOC(C)=O.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(C)C=CC=CC=1>[C:35]([O:62][C:22](=[O:24])[C:12]1[CH:7]=[CH:8][CH:9]=[C:10]([N:54]([CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[CH2:52][CH3:53])[C:11]=1[N:13]1[CH2:17][CH2:16][CH2:15][C:14]1=[O:18])([CH3:40])([CH3:36])[CH3:34]

Participants

9

Reactant 5

HCID 962WaterHCID 84352N-EthylbenzylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 69358761HCID 69358761, compound

Product 1

HCID 69357176HCID 69357176, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A flask was charged under nitrogen with 3-bromo-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (D9b) (4.6 g, 13 mmol, 1 equiv), sodium tert-butoxide (1.9 g, 19.5 mmol, 1.5 equiv), tris(dibenzylideneacetone)dipalladium(0) (395 mg, 0.65 mmol, 0.05 equiv), 2-(dicyclohexylphosphino)biphenyl (341 mg, 0.97 mmol, 0.075 equiv) and toluene (100 ml). N-Ethylbenzylamine (2.9 ml, 19.5 mmol, 1.5 equiv) was then added via syringe and the resulting mixture was stirred at 90° C. for 2 h then cooled to room temperature, diluted with H2O and AcOEt. The layers were separated, the aqueous phase diluted with saturated aqueous NaHCO3 solution and extracted with AcOEt. The combined organic phases were dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 1/2) gave (benzyl-ethyl-amino)-(2-oxo-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (D30) (3 g, 60%) as a white solid. [M+H]+=395.0, RT=3.70 min.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe layers were separated
  3. additionthe aqueous phase diluted with saturated aqueous NaHCO3 solution
  4. extractionextracted with AcOEt
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 1/2)

Sources & evidence

ORD record
ord-fee28d37134c45488134fcb826761c2e
Source dataset
uspto-grants-2007_08
Patent number
US07253198B2

Reaction notes

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