Acetic Acid → HCID 68779108, compound

HRID 2264507Notes

Reaction equation

HRID 2264507 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[CH:19][C:18](Br)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:23]1.C([O-])(=O)C.[K+].C(O)(=O)C.OO.O>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[CH:19][C:18]([OH:23])=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 962WaterHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 68781024HCID 68781024, compound

Product 1

HCID 68779108HCID 68779108, compoundYield 66.5%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 4-(5-bromo-pyrimidin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (12.4 g, 34.8 mmol, 1.0 equiv) in dioxane (100 mL) was added bis(pinacolato)diboron (13.25 g, 52.2 mmol, 1.5 equiv) and potassium acetate (10.4 g, 105 mmol, 3.0 equiv). After 15 min, bis(triphenylphosphine) palladium(II) chloride (1.47 g, 2.1 mmol, 0.06 equiv) was added and the reaction mixture was warmed up to 90° C. After 3 h, the reaction mixture was cooled down to 0° C. and glacial acetic acid (3.02 mL, 3.17 g, 52.2 mmol, 1.5 equiv) was added, followed by a solution of 30% hydrogen peroxide in water (6.58 mL, 7.44 g, 76.5 mmol, 1.5 equiv) and then warmed up to rt. After 16 h, the reaction mixture was poured into ice water and extracted twice with dichloromethane. The combined organic layers were washed with brine and water, dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 6.81 g (66%) of the title compound as yellow foam. MS (ISP): 295.3 [M+H]+.

Workup

  1. waitAfter 3 h
  2. temperaturethe reaction mixture was cooled down to 0° C.
  3. temperaturewarmed up to rt
  4. waitAfter 16 h
  5. extractionextracted twice with dichloromethane
  6. washThe combined organic layers were washed with brine and water
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated by evaporation under reduced pressure
  10. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-efcc3e9db0674148bc7a1aa05705e0e1
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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