Potassium Phosphate, Tribasic → HCID 86711854, compound

HRID 623769Notes

Reaction equation

HRID 623769 reaction equation
[CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11](Br)[C:10]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:9]1[C:25]([N:27]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:28])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:34]1(B(O)O)[CH2:36][CH2:35]1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11]([CH:34]2[CH2:36][CH2:35]2)[C:10]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:9]1[C:25]([N:27]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:28])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86711855HCID 86711855, compound

Product 1

HCID 86711854HCID 86711854, compoundYield 99.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1-benzyl-4-bromo-3-(4-chlorophenyl)-N-(2,2-dimethylpropyl)-N-methyl-5-(trifluoromethyl)pyrrole-2-carboxamide (100 mg, 0.18 mmol) in Toluene (1 mL) was added cyclopropylboronic acid (2 equiv., 0.032 g, 0.37 mmol), Palladium(II) acetate (0.1 equiv., 0.004 g, 0.018 mmol), 2-(DICYCLOHEXYLPHOSPHINO)-2′,4′,6′-TRI-I-PROPYL-1,1′-BIPHENYL (0.2 equiv., 0.01796 g, 0.03691 mmol) and POTASSIUM PHOSPHATE TRIBASIC (3 equiv., 0.1212 g, 0.04726 mL, 0.5537 mmol) in a Reactivial. The reaction was heated to 120° C. overnight. Work up: Reaction mixture cooled to room temperature and diluted with Ethyl Acetate. Filtered through celite and celite washed, through 3× Ethyl Acetate. Organics reduced under vacuum to residue. Purification: Purified via 25 g Silica Column using 0-100% Petrol Ether/(10% Ethyl Acetate/Petrol Ether) over 30 minutes collecting at 254 nm. Major peak isolated and reduced under vacuum to yield ˜90 mg (45%) white foam. Purified further via preparative HPLC using 70-95% acetonitrile/water (0.1% formic acid) over 20 min collecting at 254 nm. Pure fractions combined and reduced under vacuum.

Workup

  1. customReaction mixture
  2. temperaturecooled to room temperature
  3. filtrationFiltered through celite and celite
  4. washwashed, through 3× Ethyl Acetate
  5. customPurification
  6. customPurified via 25 g Silica Column
  7. customover 30 minutes
  8. customcollecting at 254 nm
  9. customMajor peak isolated

Sources & evidence

ORD record
ord-044834abdd9b4078bbf05cfaa0680ade
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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