4-Methoxycarbonylphenylboronic acid → 3',5'-Dichloro-4'-(1-oxo-2-aza-spiro[4.5]dec-2-ylmethyl)-biphenyl-4-carboxylic acid methyl ester

HRID 2427476Notes

Reaction equation

HRID 2427476 reaction equation
Br[C:2]1[CH:19]=[C:18]([Cl:20])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C:9]3([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:8]2=[O:17])=[C:4]([Cl:21])[CH:3]=1.[CH3:22][O:23][C:24]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)=[O:25]>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>[CH3:22][O:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([C:2]2[CH:19]=[C:18]([Cl:20])[C:5]([CH2:6][N:7]3[CH2:11][CH2:10][C:9]4([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]4)[C:8]3=[O:17])=[C:4]([Cl:21])[CH:3]=2)=[CH:28][CH:27]=1)=[O:25]

Participants

7

Reactant 2

HCID 27343694-Methoxycarbonylphenylboronic acidHCID 248637462-(4-Bromo-2,6-dichloro-benzyl)-2-aza-spiro[4.5]decan-1-one

Product 1

HCID 248637483',5'-Dichloro-4'-(1-oxo-2-aza-spiro[4.5]dec-2-ylmethyl)-biphenyl-4-carboxylic acid methyl esterYield 64%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

Purge with N2 a mixture of 2-(4-bromo-2,6-dichloro-benzyl)-2-aza-spiro[4.5]decan-1-one (0.14 g, 0.36 mmol) and 4-methoxycarbonyl phenylboronic acid (0.19 g, 1.05 mmol) in toluene (10 mL) and 2M sodium carbonate (1.25 mL). Treat the reaction with Pd(PPh3)4 (0.041 g, 0.035 mmol) and heat to 90° C. for 4 hours under N2. Cool the reaction and dilute with ethyl acetate, and then wash with 1N HCl and water. Dry the organic layer with Na2SO4 and remove the solvent in vacuo to afford crude product. Purify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel to afford 0.102 g (64%) of the titled product. Rf=0.51 (1/1 hexanes/ethyl acetate). MS (m/z): 446

Workup

  1. customPurge with N2
  2. additionTreat
  3. temperatureCool
  4. customthe reaction
  5. washwash with 1N HCl and water
  6. dry with materialDry the organic layer with Na2SO4
  7. customremove the solvent in vacuo
  8. customto afford crude product
  9. customPurify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel

Sources & evidence

ORD record
ord-2597bae66b754075b52edefabcd8e11f
Source dataset
uspto-grants-2011_06
Patent number
US07968585B2

Reaction notes

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