2-Bromonaphthalene → HCID 10787310, compound

HRID 1274147Notes

Reaction equation

HRID 1274147 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=1.[C:18]([O:22][C:23](=[O:37])[C:24]1[CH:29]=[CH:28][C:27]([NH:30][CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:26][CH:25]=1)([CH3:21])([CH3:20])[CH3:19]>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].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:18]([O:22][C:23](=[O:37])[C:24]1[CH:29]=[CH:28][C:27]([NH:30][CH:31]2[CH2:36][CH2:35][N:34]([C:8]3[CH:17]=[CH:16][C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[CH:9]=3)[CH2:33][CH2:32]2)=[CH:26][CH:25]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

8

Reactant 3

HCID 113722-BromonaphthaleneHCID 106362074-(Piperidin-4-ylamino)benzoic Acid tert-Butyl EsterHCID 23676156Sodium t-butoxide

Product 1

HCID 10787310HCID 10787310, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

Sodium tert-butoxide (0.4 g, 4 mmol) was added to a solution of 2-bromonaphthalene (0.3 g, 1.48 mmol) and 49 (0.4 g, 1.48 mmol) in 5 mL of anhydrous toluene at 25° C. Tris(dibenzylideneacetone)-dipalladium (0) (6 mg, 0.007 mmol) and (+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl [(±)-BINAP] (12.4 mg, 0.02 mmol) were added sequentially. The reaction mixture was heated to 80° C. and maintained at that temperature for 12 h, then was cooled to 25° C. and diluted with a mixture of CH3OH/CH2Cl2 (150 mL, v/v, 50:50). The diluted mixture was filtered through celite and the filtrate was concentrated in vacuo. The resulting residue was partitioned between CH2Cl2 (150 mL) and H2O (150 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 0 to 25% EtOAc in hexanes) provided the title compound (0.35 g, 59%): TLC (Rf =0.80; 40% EtOAc/hexanes); 1H NMR (CDCl3) δ 7.83 (d, 2H, J=8.4), 7.70 (m, 3H), 7.32 (m, 3H), 7.15 (d, 1H, J=2.1), 6.56 (d, 2H, J=8.7), 4.02 (d, 1H, J=7.8), 3.76 (d, 2H, J=12.7), 3.54 (m, 1H), 2.98 (t, 2H, J=12.0), 2.20 (d, 2H, J=10.7), 1.67 (m, 2H), 1.57 (s, 9H); 13C NMR (CDCl3) δ 166.0, 150.4, 149.1, 134.7, 131.5, 128.7, 128.5, 127.4, 126.7, 126.3, 123.4, 120.6, 119.8, 111.9, 110.7, 79.8, 49.6, 48.8, 32.1, 28.4; HRMS (FAB) m/z 402.2321 (M)+ (C26H30N2O2 requires 402.2307).

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 in vacuo
  5. customThe resulting residue was partitioned between CH2Cl2 (150 mL) and H2O (150 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 0 to 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-93f39d4fb9bc4c8bba4ab3840acdbda1
Source dataset
uspto-grants-2000_12
Patent number
US06156758

Reaction notes

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