2-Chloroquinoline → HCID 67401412, compound

HRID 913091Notes

Reaction equation

HRID 913091 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].O(C(C)(C)C)[K]>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 119282-ChloroquinolineHCID 12682914-Amino-1-Boc-piperidineHCID 178418922HCID 178418922, compound

Product 1

HCID 67401412HCID 67401412, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of 2-chloro-quinoline (1.00 g, 6.11 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.47 g, 7.33 mmol, 1.2 equiv; commercially available) in dimethoxyethane (15 mL) was added KOtert-Bu (0.96 g, 8.56 mmol, 1.4 equiv), (R)-(−)-1-[(S)-2-(dicyclohexyl-phosphino)-ferrocenyl]ethyl-di-tert-butylphosphine (3.39 mg, 0.0061 mmol, 0.1 mol %; Josiphos ligand [CAS RN 158923-11-6]; commercially available from Strem Chemicals, USA) and palladium(II) acetate (1.37 mg, 0.0061 mmol, 0.1 mol %). The reaction mixture was stirred at 90° C. for 4 h, concentrated by evaporation under reduced pressure and the residue purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane (+1% triethylamine)/ethyl acetate providing 1.0 g (50%) of the title compound. 1H NMR (300 MHz, DMSO): δ 1.28-1.41 (m, 2H), 1.42 (s, 9H), 1.93-1.94 (m, 2H), 2.95-3.02 (m, 2H), 3.87-3.92 (m, 2H), 4.11-4.19 (m, 1H), 6.74 (d, J=8.9 Hz, 1H), 6.94 (d, J=7.6 Hz, 1H), 7.10-7.16 (m, 1H), 7.42-7.51 (m, 2H), 7.59 (d, J=7.6 Hz, 1H), 7.83 (d, J=8.9 Hz, 1H). 13C NMR (75 MHz, DMSO): δ 28.07, 31.49, 42.41, 46.52, 78.52, 113.21, 121.03, 122.80, 125.52, 127.42, 128.89, 136.18, 147.82, 153.92, 156.13. MS (ISP): 328.5 [M+H]+.

Workup

  1. concentrationconcentrated by evaporation under reduced pressure
  2. customthe residue purified by silica column chromatography
  3. washeluting with a gradient of heptane (+1% triethylamine)/ethyl acetate providing 1.0 g (50%) of the title compound

Sources & evidence

ORD record
ord-0e2a6ef3f4534a36bb52280cdeb4e177
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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