2-Bromopyridine → 2-(4-Boc-Aminopiperidino)pyridine

HRID 1485578Notes

Reaction equation

HRID 1485578 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.Br[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 79732-Bromopyridine2×HCID 10796Cesium carbonate2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 7238334-(N-Boc-amino)piperidine

Product 1

HCID 537924442-(4-Boc-Aminopiperidino)pyridineYield 312.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

The reaction mixture of tert-butyl piperidin-4-ylcarbamate (200 mg, 0.10 mmol), 2-bromopyridine (205 mg, 1.30 mmol), Pd2(dba)3 (18.0 mg, 0.02 mmol), Xantphos (35.0 mg, 0.06 mmol) and Cs2CO3 (490 mg, 1.50 mmol) was heated at 100° C. for 1 day. Additional 2-bromopyridine (205 mg, 1.30 mmol), Pd2(dba)3 (18.0 mg, 0.02 mmol), Xantphos (35.0 mg, 0.06 mmol), Cs2CO3 (490 mg, 1.50 mmol) were added to the reaction mixture, and heated at 100° C. for 1 day. The reaction mixture was cooled to room temperature, diluted with EtOAc and water. The separated aqueous layer was extracted with EtOAc, the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (EtOAc) to give tert-butyl 1-(pyridin-2-yl)piperidin-4-ylcarbamate (86.8 mg, 31%) as a pale yellow solid. m/z=278.06 [M+1]+.

Workup

  1. temperatureheated at 100° C. for 1 day
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionThe separated aqueous layer was extracted with EtOAc
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (EtOAc)

Sources & evidence

ORD record
ord-0faf886d2d404b4ca2410786ceeae1bc
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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