Potassium Phosphate, Tribasic → HCID 58129453, compound

HRID 1969454Notes

Reaction equation

HRID 1969454 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13](Br)[N:12]=1)([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH:19]1(B(O)O)[CH2:21][CH2:20]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH:19]2[CH2:21][CH2:20]2)[N:12]=1)([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2760897Cyclopropylboronic acidHCID 581294981,1-Dimethylethyl N-[1-(6-bromo-2-pyridinyl)-1-methylethyl]carbamate

Product 1

HCID 58129453HCID 58129453, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

Combine [1-(6-bromo-pyridin-2-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester (1.64 g, 7.6 mmol), cyclopropyl boronic acid (850 mg, 9.9 mmol), potassium phosphate (6.1 g, 26.6 mmol), and palladium acetate (85 mg, 0.38 mmol). Add toluene (31 mL) and water (1.4 mL) followed by 1M tricyclohexyl phosphine in toluene (760 μl, 0.76 mmol); degas the mixture, purge with nitrogen, and heat at 100° C. for 6 hours, then stir at room temperature overnight. Add tri tert-butylphosphine (153 mg, 0.76 mmol) and palladium acetate (85 mg, 0.38 mmol), degas and heat at 85° C. overnight. Filter the reaction and purify the filtrate over silica (120 g) eluting with 0% to 25% EtOAc:hexanes to give [1-(6-cyclopropyl-pyridin-2-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester as an oily yellow solid (1.3 g, 62%). MS (m/z): 277.4 (M+H)+.

Workup

  1. customdegas the mixture
  2. custompurge with nitrogen
  3. temperatureheat at 85° C. overnight
  4. filtrationFilter
  5. customthe reaction
  6. custompurify the filtrate over silica (120 g)
  7. washeluting with 0% to 25% EtOAc

Sources & evidence

ORD record
ord-54e7c8aa75e14198a4f64e5204c1a521
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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