Nitrogen → 3',5'-Dichloro-4'-(2-oxo-3-piperidin-1-yl-pyrrolidin-1-ylmethyl)-biphenyl-4-carboxylic acid methyl ester

HRID 1670843Notes

Reaction equation

HRID 1670843 reaction equation
Br[C:2]1[CH:20]=[C:19]([Cl:21])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[C:8]2=[O:18])=[C:4]([Cl:22])[CH:3]=1.[CH3:23][O:24][C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)=[O:26].N#N>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:23][O:24][C:25]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:20]=[C:19]([Cl:21])[C:5]([CH2:6][N:7]3[CH2:11][CH2:10][CH:9]([N:12]4[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]4)[C:8]3=[O:18])=[C:4]([Cl:22])[CH:3]=2)=[CH:29][CH:28]=1)=[O:26]

Participants

8

Reactant 3

HCID 947NitrogenHCID 27343694-Methoxycarbonylphenylboronic acidHCID 576580161-(4-Bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one

Product 1

HCID 576580003',5'-Dichloro-4'-(2-oxo-3-piperidin-1-yl-pyrrolidin-1-ylmethyl)-biphenyl-4-carboxylic acid methyl esterYield 39%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
90 °C

Procedure

Purge a mixture of 1-(4-bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one (0.429 g, 1.06 mmol) and 4-methoxycarbonyl phenylboronic acid (0.57 g, 3.16 mmol) in toluene (15 mL) and 2M sodium carbonate (3.7 mL) with N2. Treat the reaction with Pd(PPh3)4 (0.061 g, 0.053 mmol) and heat to 90° C. for 7 hours under N2. Cool the reaction, dilute with ethyl acetate, and wash with water. Dry the organic layer (Na2SO4), remove the solvent in vacuo afford crude product, and purify with a 0 to 10% methanol in CH2Cl2 gradient to afford 0.19 g (39%) of the titled product. Rf=0.40 (9/1 CH2Cl2/methanol). ES MS (m/z): 461 (M+).

Workup

  1. customPurge
  2. additionTreat
  3. temperatureCool
  4. customthe reaction
  5. washwash with water
  6. dry with materialDry the organic layer (Na2SO4)
  7. customremove the solvent in vacuo
  8. customafford crude product
  9. custompurify with a 0 to 10% methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-9c6de28b02c245a9ad8e45e0f7fd1b18
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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