Potassium Carbonate → 1,1-Dimethylethyl 4-[(6-amino-3-pyridinyl)methyl]-1-piperidinecarboxylate

HRID 2264358Notes

Reaction equation

HRID 2264358 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C12BC(CCC1)CCC2.[NH2:24][C:25]1[CH:30]=[CH:29][C:28](Br)=[CH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>[Pd](Cl)Cl.CC(=O)OCC.O.CN(C=O)C.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:28]2[CH:27]=[N:26][C:25]([NH2:24])=[CH:30][CH:29]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 706222-Amino-5-bromopyridineHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-Methylenepiperidine

Product 1

HCID 674268661,1-Dimethylethyl 4-[(6-amino-3-pyridinyl)methyl]-1-piperidinecarboxylateYield 28.9%

Reagents, catalysts & solvents 5

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

Stir for 5 min 4-methylene-piperidine-1-carboxylic acid tert-butyl ester (5.10 g) under nitrogen and add a 0.5 M THF solution of 9-borabicyclo[3.3.1]nonane (77.49 mL). Stir at 75° C. under nitrogen for 1 h. Cool and add 2-amino-5-bromopyridine (3.8 g), potassium carbonate (3.87 g), and 1,1′-biss(diphenylphosphino)ferrocene)palladium(II) chloride (538.10 mg) and a degassed mixture of DMF (47.83 mL) and water (4.78 mL). Stir at 60° C. during 4 h, then at RT over the weekend. Add water and EA. Separate and extract aqueous layer with EA. Combine the organic layers and dry over sodium sulfate and remove the solvent under vacuum. Purify by silica gel column chromatography, eluting with DCM/methanol (1%)/ammonia (0.1%) to DCM/methanol (3%)/ammonia (0.3%). Triturate the residue with EA to afford 1.85 g of the title compound. MS (ES+): m/z=292 (M+H)+.

Workup

  1. temperatureCool
  2. stirringStir at 60° C. during 4 h
  3. customat RT
  4. customSeparate
  5. extractionextract aqueous layer with EA
  6. dry with materialdry over sodium sulfate
  7. customremove the solvent under vacuum
  8. customPurify by silica gel column chromatography
  9. washeluting with DCM/methanol (1%)/ammonia (0.1%) to DCM/methanol (3%)/ammonia (0.3%)
  10. customTriturate the residue with EA

Sources & evidence

ORD record
ord-3bf9205bb1444cfba15d1e598378e164
Source dataset
uspto-grants-2010_12
Patent number
US07855211B2

Reaction notes

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