Binap, (A+-)- → 4-(8-Chloro-quinolin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 913097Notes

Reaction equation

HRID 913097 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([Cl:12])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].O(C(C)(C)C)[K].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH:26][C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[C:5]([Cl:12])[CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 6765532,8-DichloroquinolineHCID 12682914-Amino-1-Boc-piperidineHCID 178418922HCID 178418922, compound

Product 1

HCID 673978104-(8-Chloro-quinolin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2,8-dichloro-quinoline (3.00 g, 15.15 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (3.64 g, 18.18 mmol, 1.2 equiv; commercially available) in toluene (35 mL) was added KOtert-Bu (2.38 g, 21.21 mmol, 1.4 equiv), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.38 g, 0.61 mmol, 0.04 equiv) and tris(dibenzylideneacetone)-dipalladium(0) (0.31 g, 0.30 mmol, 0.02 equiv). The reaction mixture was stirred at 80° C. for 18 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 1.73 g (31%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.37-1.51 (m, 2H), 1.48 (s, 9H), 2.17-2.22 (m, 2H), 2.96-3.04 (m, 2H), 4.07-4.17 (m, 3H), 4.76 (d, J=7.0 Hz, 1H), 6.64 (d, H=8.9 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.64 (d, J=7.8 Hz, 1H), 7.80 (d, J=8.9 Hz, 1H). MS (ISP): 362.5 [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 1.73 g (31%) of the title compound

Sources & evidence

ORD record
ord-dba02257a94f47c6a035bf98033da441
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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