Phosphine → HCID 68671282, compound

HRID 1773384Notes

Reaction equation

HRID 1773384 reaction equation
P.[C:2]([O:6][C:7](=[O:18])[C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:5])([CH3:4])[CH3:3].[CH3:19][N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][OH:26]>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].C1(C)C=CC=CC=1>[CH3:19][N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][O:26][C:11]1[CH:12]=[CH:13][C:8]([C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:18])=[C:9]([N+:15]([O-:17])=[O:16])[CH:10]=1

Participants

6

Reactant 3

HCID 24404PhosphineHCID 643492(2S)-1-Methyl-2-pyrrolidinemethanolHCID 26369829tert-Butyl 4-bromo-2-nitrobenzoate

Product 1

HCID 68671282HCID 68671282, compoundYield 41.1%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a round bottomed three neck flask under argon atmosphere were added toluene (15 ml), CsCO3 (1.6 gr, 5 mmol), phosphine ligand 2-(di-tert-butylphosphino)-1,1′-binaphthyl (331 mg, 0.83 mmol) and Pd(dba)2 (380 mgr, 0.66 mmol). The mixture was degassed bubbling argon for five minutes. Then 4-bromo-2-nitrobenzoic acid tert butyl ester (1 gr, 3.31 mmol) and (S)-(−)-1-methyl-2-pyrrolidinemethanol (0.78 ml, 6.62 mmol) were added and the mixture was heated to 100° C. for 18 hr. The reaction was cooled to room temperature, quenched with 30 ml of water and extracted twice with 25 ml of AcOEt. The organic phases were collected, dried over Na2SO4 and the solvents evaporated to obtain a red oil which was subjected to chromatography purification on a Biotage SP1 automated system (90:10 DCM/MeOH (isocratic) to yield the pure title compound as a yellowish oil (460 mgr, 1.36 mmol, 41% yield).

Workup

  1. customThe mixture was degassed
  2. custombubbling argon for five minutes
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with 30 ml of water
  5. extractionextracted twice with 25 ml of AcOEt
  6. customThe organic phases were collected
  7. dry with materialdried over Na2SO4
  8. customthe solvents evaporated
  9. customto obtain a red oil which
  10. customwas subjected to chromatography purification on a Biotage SP1 automated system (90:10 DCM/MeOH (isocratic)

Sources & evidence

ORD record
ord-75b66963b83b483e8fe302f8c9a6b10b
Source dataset
uspto-grants-2016_02
Patent number
US09255087B2

Reaction notes

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