Sodium Bicarbonate → Di-tert-butyl (2s,2's)-2,2'-(4,4'-biphenyldiylbis(1h-imidazole-5,2-diyl))di(1-pyrrolidinecarboxylate)

HRID 1185628Notes

Reaction equation

HRID 1185628 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][CH:21]1[C:25]1[NH:26][C:27]([C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[C:32](C(OC)=O)[CH:31]=2)=[CH:28][N:29]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(=O)(O)[O-].[Na+]>O.CCOC(C)=O.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:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:25]1[NH:26][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:33]3[CH:32]=[CH:31][C:30]([C:27]4[NH:26][C:25]([CH:21]5[CH2:22][CH2:23][CH2:24][N:20]5[C:18]([O:17][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:19])=[N:29][CH:28]=4)=[CH:35][CH:34]=3)=[CH:32][CH:31]=2)=[CH:28][N:29]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 643455N-Boc-pyrrolidineHCID 666201422-{5-[3-Methoxycarbonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 25230004Di-tert-butyl (2s,2's)-2,2'-(4,4'-biphenyldiylbis(1h-imidazole-5,2-diyl))di(1-pyrrolidinecarboxylate)Yield 105%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To the solution of 245-{4-bromo-3-[(tert-butoxycarbonyl-methyl-amino)-methyl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (142 mg, 0.27 mmol) and 2-{5-[3-Methoxycarbonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (125 mg, 0.25 mmol) in 1,2-dimethoxyether (2.3 ml) and water (0.7 ml) was added sodium bicarbonate (63 mg, 0.75 mmol), followed by Pd(PPh3)4 (12 mg) and PdCl2(dppf)CH2Cl2 (12 mg). The mixture was heated at 80° C. for 20 hours. The mixture was diluted with EtOAc, and was washed with water and brine, and was dried with sodium sulfate. Concentration and purification by flash column chromatography (hexanes/EtOAc) gave 4,4′-bis-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-biphenyl-2-[(tert-butoxycarbonyl-methyl-amino)-2′-carboxylic acid dimethyl ester (82 mg). m/z: 826 (M+H)+, 413.6 (M+2H)+/2.

Workup

  1. washwas washed with water and brine
  2. dry with materialwas dried with sodium sulfate
  3. concentrationConcentration and purification by flash column chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-d2ef22574e074269850562bd639970ef
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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