4-Amino-1-Boc-piperidine → HCID 67195387, compound

HRID 547912Notes

Reaction equation

HRID 547912 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](I)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH: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(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1(C)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH:26][C:6]2[C:5]3[C:10](=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=[CH:8][CH:7]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 12682914-Amino-1-Boc-piperidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 111853697-Chloro-4-iodoquinolineHCID 178418922HCID 178418922, compound

Product 1

HCID 67195387HCID 67195387, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 7-chloro-4-iodo-quinoline (5.33 g, 18.42 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.43 g, 22.11 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (5.17 g, 46.06 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.18 g, 0.37 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone) dipalladium(0) (1.53 g, 1.47 mmol, 0.08 equiv). The reaction mixture was stirred under nitrogen at 100° C. for 16 h, cooled to rt, filtered and the filtrate concentrated by evaporation under reduced pressure. The crude material was purified with silica column chromatography eluting with dichloromethane/methanol (20:1+0.5% triethylamine) and then recrystallized from heptane/ethyl acetate to provide 2.20 g (33%) of the title compound in 80% purity according to 1H NMR. 1H NMR (250 MHz, DMSO): δ 1.42 (s, 9H), 1.46-1.61 (m, 2H), 1.94 (d, J=10.3 Hz, 2H), 2.75-3.03 (m, 2H), 3.88 (br s, 1H), 3.94-4.14 (m, 2H), 6.75 (d, J=6.1 Hz, 1H), 7.56 (d, J=6.9 Hz, 2H), 7.82 (s, 1H), 8.31-8.55 (m, 2H). MS (ESI): 362.2 [M+H]+.

Workup

  1. temperaturecooled to rt
  2. filtrationfiltered
  3. concentrationthe filtrate concentrated by evaporation under reduced pressure
  4. customThe crude material was purified with silica column chromatography
  5. washeluting with dichloromethane/methanol (20:1+0.5% triethylamine)
  6. customrecrystallized from heptane/ethyl acetate

Sources & evidence

ORD record
ord-8b4becb02118424fa4915c03a8c979a3
Source dataset
uspto-grants-2011_05
Patent number
US07939661B2

Reaction notes

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