Ethyl Acetate → Trifluoro-methanesulfonic acid 3-(3,5-Dichloro-4'-carboxymethyl-biphenyl-4-ylmethyl)-1-(4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-2-one

HRID 1013793Notes

Reaction equation

HRID 1013793 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:32][S:33]([C:36]([F:39])([F:38])[F:37])(=[O:35])=[O:34])[CH:5]=[C:6]([Cl:31])[C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:22][CH2:21][C:20]3[C:16](=[CH:17][N:18](S(C(F)(F)F)(=O)=O)[N:19]=3)[CH2:15]2)[C:10]1=[O:30].[C:40]([CH2:43][C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1)([OH:42])=[O:41].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.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.C(Cl)Cl.CO.O>[Cl:31][C:6]1[CH:5]=[C:4]([C:47]2[CH:48]=[CH:49][C:44]([CH2:43][C:40]([OH:42])=[O:41])=[CH:45][CH:46]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:22][CH2:21][C:20]3[C:16](=[CH:17][NH:18][N:19]=3)[CH2:15]2)[C:10]1=[O:30].[F:37][C:36]([F:39])([F:38])[S:33]([OH:35])(=[O:34])=[O:32]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 218789612-(4-Boronophenyl)acetic acidHCID 57671341Trifluoro-methanesulfonic acid 3,5-dichloro-4-[2-oxo-1-(2-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-3-ylmethyl]-phenyl ester

Product 1

HCID 178525017Trifluoro-methanesulfonic acid 3-(3,5-Dichloro-4'-carboxymethyl-biphenyl-4-ylmethyl)-1-(4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-2-one

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Combine Trifluoro-methanesulfonic acid 3,5-dichloro-4-[2-oxo-1-(2-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (1.0 g, 1.55 mmol), 4-Carboxymethylphenyl boronic acid (0.416 g, 2.3 mmol), sodium carbonate (2.3 ml of 2.0 M, 5.4 mmol) in DME (12 mL) and degas with a stream of nitrogen. Add (Ph3P)4Pd (0.078 g, 0.15 mmol), and stir at 80° C. for 17 hour under nitrogen atmosphere. Cool to ambient temperature and add ethyl acetate (20 mL) and water (10 mL). Extract the aqueous phase with ethyl acetate (2×20 mL), dry (sodium sulfate) and condense under reduced pressure. Chromatography (silica, 95:5 CH2Cl2/Methanol) yields 0.750 g as a white solid MS (m/z): 632 (M+2).

Workup

  1. extractionExtract the aqueous phase with ethyl acetate (2×20 mL)
  2. customdry
  3. custom(sodium sulfate) and condense under reduced pressure

Sources & evidence

ORD record
ord-8633ddc908174e9f99429ad127dd93d5
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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