Methanol → HCID 178432841, compound

HRID 1625502Notes

Reaction equation

HRID 1625502 reaction equation
I[C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][C@H:10]([CH3:12])[CH2:9][N:8]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[N:4][C:3]=1[CH3:20].CO.[Br:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=2)=[CH:26][CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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>[Br:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:2]3[NH:6][C:5]([C@@H:7]4[CH2:11][C@H:10]([CH3:12])[CH2:9][N:8]4[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[N:4][C:3]=3[CH3:20])=[CH:32][CH:31]=2)=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 38416074'-Bromo-4-biphenylboronic Acid (contains varying amounts of Anhydride)HCID 178432842HCID 178432842, compound

Product 1

HCID 178432841HCID 178432841, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butyl (2S,4S)-2-(5-iodo-4-methyl-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (289 mg, 0.7387 mmol) in 6 mL of 5:1 toluene:methanol is sequentially added [4-(4-bromophenyl)phenyl]boronic acid (346.7 mg, 1.252 mmol), K3PO4 (199.3 mg, 0.9389 mmol) and Pd(PPh3)4 (71.85 mg, 0.06218 mmol). The reaction mixture is heated at 75° C. for 3 hours. The reaction mixture is concentrated, diluted with ethyl acetate, and washed with water and brine. The organic layer is concentrated to dryness. The residue is dissolved in dichloromethane and purified by flash column chromatography on silica gel (0-10% methanol/dichloromethane) to give (2S,4S)-tert-butyl 2-(5-(4′-bromo-[1,1′-biphenyl]-4-yl)-4-methyl-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (160 mg, 0.322 mmol).

Workup

  1. concentrationThe reaction mixture is concentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with water and brine
  4. concentrationThe organic layer is concentrated to dryness
  5. dissolutionThe residue is dissolved in dichloromethane
  6. custompurified by flash column chromatography on silica gel (0-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-61ba7214911b4dfaab004bce7829ec80
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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