Cesium carbonate → HCID 10520033, compound

HRID 1274118Notes

Reaction equation

HRID 1274118 reaction equation
BrC[C:3]1[CH:11]=[CH:10][C:6]([C:7]([O-:9])=[O:8])=[CH:5][CH:4]=1.[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:15][CH2:14]1.[C:26]1(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.CO.C(Cl)Cl.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]>[CH3:26][O:9][C:7](=[O:8])[C:6]1[CH:5]=[CH:4][C:3]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)=[CH:11][CH:10]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 4158521-Benzyl-4-piperidylamineHCID 634876Binap, (A+-)-HCID 6919881HCID 6919881, compound

Product 1

HCID 10520033HCID 10520033, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

4-Bromomethylbenzoate (4.3 g, 20 mmol) was dissolved in 40 mL of anhydrous toluene. 4-Amino-1-benzyl piperidine (4.8 mL, 22 mmol), tris(dibenzylideneacetone)-dipalladium(0) (60 mg, 0.07 mmol), (±)-2,2'-bis(diphenyl-phosphino)-1,1'-binaphthyl [(±)-BINAP] (124 mg, 0.2 mmol) and cesium carbonate (9.2 g, 28 mmol) were added sequentially at 25° C. The resulting mixture was stirred and heated to 80° C., maintained at that temperature for 12 h, then was cooled to 25° C. The reaction mixture was diluted with a mixture of MeOH/CH2Cl2 (150 mL, v/v, 50:50). The diluted mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The resulting residue was partitioned between EtOAc (200 mL) and H2O (200 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a deep yellow solid residue. Purification of the residue by flash column chromatography (gradient elution 30 to 40% EtOAc in hexanes) provided the title compound as a pale yellow solid residue (2.26 g, 35%): TLC (Rf =0.40; 60% EtOAc/hexanes); 1H NMR (CDCl3) δ 7.84 (d, 2H, J=8.8), 7.31 (s, 5H), 6.52 (d, 2H, J=8.9), 4.04 (d, 1H, J=7.8), 3.84 (s, 3H), 3.53 (s, 2H), 3.40 (m, 1H), 2.85 (d, 2H, J=11.9), 2.16 (t, 2H, J=12.7), 1.99 (m, 2H), 1.52 (m, 2H); 13C NMR (CDCl3) δ 167.3, 150.9, 138.2, 131.6, 129.1, 128.2, 127.1, 118.0, 111.7, 63.1, 52.1, 51.5, 49.5, 32.3; Anal. (C20H24N2O2) C, H, N.

Workup

  1. temperaturemaintained at that temperature for 12 h
  2. temperaturewas cooled to 25° C
  3. filtrationThe diluted mixture was filtered through celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was partitioned between EtOAc (200 mL) and H2O (200 mL)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a deep yellow solid residue
  10. customPurification of the residue
  11. washby flash column chromatography (gradient elution 30 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1e5e15dae6ae478c9995e57dc38467ab
Source dataset
uspto-grants-2000_12
Patent number
US06156758

Reaction notes

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