4-Chloro-2-formylphenylboronic Acid (contains varying amounts of Anhydride) → 2-[5-(4-Chloro-2-formyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71927Notes

Reaction equation

HRID 71927 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15](Br)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[C:22]([CH:29]=[O:30])[CH:21]=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.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.COCCOC>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:23]2[CH:24]=[CH:25][C:20]([Cl:19])=[CH:21][C:22]=2[CH:29]=[O:30])=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 237304254-Chloro-2-formylphenylboronic Acid (contains varying amounts of Anhydride)HCID 56605248tert-Butyl 2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 723382662-[5-(4-Chloro-2-formyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 78%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

2-(5-Bromo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.00 g, 6.32 mmol), 4-Chloro-2-formyl-phenylboronic acid (1.17 g, 6.32 mmol), Pd(PPh3)4 (365 mg, 0.316 mmol), Pd(dppf)Cl2-DCM (258 mg, 0.316 mmol) K2CO3 (2 M, 6.3 mL, 12.6 mmol) and DME (30 mL) were combined in a round bottom flask. The stirred suspension was degassed for 10 minutes with bubbling N2 then heated to 85° C. After 4 h, the reaction mixture was poured into saturated aqueous NaHCO3. The aqueous phase was extracted 3× with EtOAc and the combined organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (25% to 75% EtOAc/Hexane) to afford the title compound 2-[5-(4-Chloro-2-formyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.85 g, 78%).

Workup

  1. customThe stirred suspension was degassed for 10 minutes with bubbling N2
  2. additionthe reaction mixture was poured into saturated aqueous NaHCO3
  3. extractionThe aqueous phase was extracted 3× with EtOAc
  4. dry with materialthe combined organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by silica column chromatography (25% to 75% EtOAc/Hexane)

Sources & evidence

ORD record
ord-87851652215e4d34b03c94f71c3afd3b
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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