Piperidine → HCID 59299346, compound

HRID 2235315Notes

Reaction equation

HRID 2235315 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11]C[N:9]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:8]2=[O:19])=[C:4]([Cl:22])[CH:3]=1.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:22][C:4]1[CH:3]=[C:2]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH:21]=[CH:20][C:5]=1[CH2:6][CH:7]1[CH2:12][CH2:11][N:9]([CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]2)[C:8]1=[O:19]

Participants

7

Reactant 4

HCID 8082PiperidineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 59299455HCID 59299455, compound

Product 1

HCID 59299346HCID 59299346, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Dissolve 3-(4-bromo-2-chloro-benzyl)-1-cyclohexyl-piperidin-2-one (Example 55) (0.20 g, 0.54 mmol), piperidine (0.21 mL, 2.16 mmol), palladium (II) acetate (12 mg, 0.05 mmol) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (67 mg, 0.11 mmol) in toluene (1 mL) with cesium carbonate (264 mg, 0.81 mmol) and heat at 90° C. 16 h. Pass the mixture through an SCX ion exchange column washing with methanol and eluting with 1N ammonia in methanol and evaporate. Purify the residue by preparative reversed phase HPLC chromatography to give the title compound (98 mg, 48%). MS (ES+) nz/z=376 (M+H)+.

Workup

  1. custom16 h
  2. washPass the mixture through an SCX ion exchange column washing with methanol
  3. washeluting with 1N ammonia in methanol
  4. customevaporate
  5. customPurify the residue by preparative reversed phase HPLC chromatography

Sources & evidence

ORD record
ord-f0ca624e26ac4bb880677439fa5c5ba4
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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