4-Amino-1-Boc-piperidine → HCID 67198335, compound

HRID 547910Notes

Reaction equation

HRID 547910 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH: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].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:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][CH:3]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 12682914-Amino-1-Boc-piperidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 117359184-bromoquinolineHCID 178418922HCID 178418922, compound

Product 1

HCID 67198335HCID 67198335, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 4-bromo-quinoline (4.00 g, 19.23 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.62 g, 23.08 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (5.40 g, 48.07 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.18 g, 0.39 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone) dipalladium(0) (1.59 g, 1.54 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 a gradient of ethyl acetate/triethylamine (10:0→20:1) to provide 3.40 g (54%) of the title compound in 90% purity according to 1H NMR. 1H NMR (400 MHz, DMSO): δ 1.39 (s, 9H), 1.55-1.70 (m, 2H), 1.93 (d, J=10.4 Hz, 2H), 2.93 (br s, 2H), 3.96-4.06 (m, 2H), 4.06-4.15 (m, 1H), 7.00 (d, J=7.0 Hz, 1H), 7.62-7.71 (m, 1H), 7.86-7.95 (m, 2H), 8.54 (d, J=6.9 Hz, 2H), 8.60 (d, J=8.6 Hz, 1H).

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 a gradient of ethyl acetate/triethylamine (10:0→20:1)

Sources & evidence

ORD record
ord-cf4f2c3eb45b477ab2d002b71a3d29d3
Source dataset
uspto-grants-2011_05
Patent number
US07939661B2

Reaction notes

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