Binap, (A+-)- → 4-(1'-Cyclopropylmethyl-2'-oxo-3,4,5,6,1',2'-hexahydro-2H-[1,4']bipyridinyl-4-yl)-benzoic acid

HRID 2276324Notes

Reaction equation

HRID 2276324 reaction equation
C[O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:64]1[CH:69]=[CH:68][N:67]([CH2:70][CH:71]2[CH2:73][CH2:72]2)[C:66](=[O:74])[CH:65]=1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:71]1([CH2:70][N:67]2[CH:68]=[CH:69][C:64]([N:13]3[CH2:14][CH2:15][CH:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:16])=[CH:5][CH:6]=4)[CH2:11][CH2:12]3)=[CH:65][C:66]2=[O:74])[CH2:72][CH2:73]1

Participants

7

Reactant 3

HCID 634876Binap, (A+-)-HCID 24904226Methyl 4-(piperidin-4-yl)benzoateHCID 585545154-Bromo-1-(cyclopropylmethyl)pyridin-2(1H)-one

Product 1

HCID 594971014-(1'-Cyclopropylmethyl-2'-oxo-3,4,5,6,1',2'-hexahydro-2H-[1,4']bipyridinyl-4-yl)-benzoic acid

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

4-Piperidin-4-ylbenzoic acid methyl ester (0.40 g, 1.81 mmol), palladium(II) acetate (0.015 g, 0.069 mmol) sodium tert-butoxide (0.34 g, 3.44 mmol) and BINAP (0.06 g, 0.096 mmol) were added to a stirred solution of intermediate D3 (0.31 g, 1.37 mmol) in toluene (10 ml). The reaction mixture was heated at 100° C. for 16 hours in a sealed tube. After cooling to room temperature the mixture was diluted with EtOAc and then filtered through diatomaceous earth, after which the solvent was evaporated in vacuo. The crude residue was treated with a mixture of DCM/methanol and then filtered off. The filtrate was evaporated to dryness in vacuo to yield crude D37 (0.48 g, 100%) that was used without further purification.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. filtrationfiltered through diatomaceous earth
  3. customafter which the solvent was evaporated in vacuo
  4. additionThe crude residue was treated with a mixture of DCM/methanol
  5. filtrationfiltered off
  6. customThe filtrate was evaporated to dryness in vacuo
  7. customto yield crude D37 (0.48 g, 100%) that
  8. customwas used without further purification

Sources & evidence

ORD record
ord-6aeb2cab14ec43cdadcf3a56086726e8
Source dataset
uspto-grants-2015_09
Patent number
US09132122B2

Reaction notes

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