Di-tert-butyl dicarbonate → HCID 68513291, compound

HRID 1716577Notes

Reaction equation

HRID 1716577 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[NH:22][C:23](=O)[C:24](OCC)([O:26]CC)[CH3:25])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C>C(O)(=O)C.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=3[N:22]=[C:23]2[C:24](=[O:26])[CH3:25])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 90495Di-tert-butyl dicarbonateHCID 68510828HCID 68510828, compound

Product 1

HCID 68513291HCID 68513291, compoundYield 68.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

4-[2-(2,2-Diethoxy-propionylamino)-4-methyl-phenylamino]-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.11 mmol) was dissolved in glacial acetic acid (5 mL), and the mixture was heated at 90° C. overnight. The mixture was cooled, concentrated under reduced pressure. The resulting residue was partitioned between CH2Cl2 (50 mL) and dilute aqueous K2CO3 solution. The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×25 mL). The combined organic layers were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to approximately 30 mL, and di-tert-butyldicarbonate (218 mg, 1 mmol) and DMAP (5 mg, 0.04 mmol) were added. The mixture was stirred overnight at rt, washed with saturated aqueous NH4Cl solution and dried over anhydrous Na2SO4. The mixture was concentrated, and the residue was purified by flash chromatography (30% ethyl acetate in hexanes) to give 4-(2-acetyl-5-methyl-benzoimidazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (270 mg, 0.756 mmol, 68%) as a waxy solid.

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting residue was partitioned between CH2Cl2 (50 mL) and dilute aqueous K2CO3 solution
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (2×25 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. additionwere added
  9. washwashed with saturated aqueous NH4Cl solution
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationThe mixture was concentrated
  12. customthe residue was purified by flash chromatography (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e166f22b364d4387a9bd530213ccc42d
Source dataset
uspto-grants-2010_09
Patent number
US07803816B2

Reaction notes

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