Morpholine → HCID 58547921, compound

HRID 454913Notes

Reaction equation

HRID 454913 reaction equation
Br[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.CC(C)([O-])C.[Na+]>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].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>[O:25]1[CH2:26][CH2:27][N:22]([C:2]2[C:3]([O:8][CH:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:23][CH2:24]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 58547976HCID 58547976, compound

Product 1

HCID 58547921HCID 58547921, compoundYield 77.7%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a solution of tert-butyl 4-((3-bromopyridin-2-yl)oxy)piperidine-1-carboxylate (see PREPARATION P20.4; 4 g, 11.2 mmol), morpholine (1.46 g, 16.8 mmol), Pd2(dba)3 (513 mg, 0.56 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (349 mg, 0.56 mmol), sodium tert-butoxide (t-BuONa) (2.15 g, 22.4 mmol) then the reaction mixture was stirred at 90° C. for overnight. The mixture was left to reach room temperature, then the reaction mixture was filtered through a pad of CELITE® and the filter cake was washed with CH2Cl2 (3×20 mL). The combined filtrates were evaporated in vacuo and the residue was purified by column chromatography to give the product (3.1 g, 8.7 mmol, yield 70%). ESI-MS (M+1): 364 calc. for C19H29N3O4 363.

Workup

  1. waitThe mixture was left
  2. customto reach room temperature
  3. filtrationthe reaction mixture was filtered through a pad of CELITE®
  4. washthe filter cake was washed with CH2Cl2 (3×20 mL)
  5. customThe combined filtrates were evaporated in vacuo
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-eca7af5c3fe04d46adef2f3909e22bfe
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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