Ethyl Acetate → 3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid methyl ester

HRID 415979Notes

Reaction equation

HRID 415979 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[C:10]1=[O:20].C(=O)([O-])[O-].[Na+].[Na+].[C:36]([CH2:39][C:40]1C=CC(B(O)O)=[CH:42][CH:41]=1)(O)=O.[C:49]([O:52][CH2:53]C)(=[O:51])[CH3:50]>C1(C)C=CC=CC=1.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>[CH3:53][O:52][C:49]([C:50]1[CH:42]=[CH:41][C:40]([C:4]2[CH:3]=[C:2]([Cl:1])[C:7]([CH2:8][CH:9]3[CH2:13][CH2:12][N:11]([CH:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[C:10]3=[O:20])=[C:6]([Cl:21])[CH:5]=2)=[CH:39][CH:36]=1)=[O:51]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 218789612-(4-Boronophenyl)acetic acidHCID 592994213,5-Dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate

Product 1

HCID 666217223',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

Dissolve trifluoro-methanesulfonic acid 3,5-dichloro-4-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-phenyl ester (5 g, 10.54 mmol) in 50 mL toluene, add aqueous 2 M sodium carbonate and evacuate/purge with nitrogen 3 times. Add p-carboxymethylphenylboronic acid (2.85 g, 15.81 mmol), degas again, then add Pd(PPh3)4 (1.22 g, 1.05 mmol). Degass/purge one more time then reflux overnight. Separate layers, wash the organic layer with water twice, then wash with brine. Dry over sodium sulfate, filter and concentrate under vacuum to yield a brown foam. Add ethyl acetate to get a tan solid and filter to get 3.8 g product. Concentrate the filtrate to recover 0.4 g more product after purification via silica gel chromatography using 25% ethyl acetate: MS (m/z): 460 (M+).

Workup

  1. customevacuate/purge with nitrogen 3 times
  2. customDegass/purge one more time
  3. temperaturethen reflux overnight
  4. washSeparate layers, wash the organic layer with water twice
  5. washwash with brine
  6. dry with materialDry over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under vacuum
  9. customto yield a brown foam
  10. filtrationfilter

Sources & evidence

ORD record
ord-6ac188397a10494fbb0412bf627cc299
Source dataset
uspto-grants-2012_01
Patent number
US08088776B2

Reaction notes

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