Potassium Phosphate, Tribasic → HCID 58129453, compound

HRID 1969453Notes

Reaction equation

HRID 1969453 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([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

8

Reactant 4

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

Product 1

HCID 58129453HCID 58129453, compoundYield 49%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

Combine [1-(6-bromo-pyridin-2-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester (250 mg, 1.16 mmol), cyclopropyl boronic acid (129 mg, 1.5 mmol), potassium phosphate (920 mg, 4.0 mmol), toluene (4.8 mL) and water (0.24 mL). Mix vigorously. Add 1M tricyclohexyl phosphine in toluene (120 μA, 0.12 mmol); degas the mixture, purge with nitrogen, and add palladium acetate 13 mg, (0.06 mmol) and heat at 100° C. for 6 hours, then stir at room temperature overnight. Filter the reaction and purify the filtrate over silica (80 g) eluting with 0% to 25% EtOAc:hexanes to give [1-(6-cyclopropyl-pyridin-2-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester (157 mg, 49%). MS (m/z): 277.3 (M+H)+.

Workup

  1. additionMix vigorously
  2. customdegas the mixture
  3. custompurge with nitrogen
  4. filtrationFilter
  5. customthe reaction
  6. custompurify the filtrate over silica (80 g)
  7. washeluting with 0% to 25% EtOAc

Sources & evidence

ORD record
ord-3c8001eec84b4e38bbddf7e8873c1171
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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