Benzoyl chloride → HCID 18967541, compound

HRID 235146Notes

Reaction equation

HRID 235146 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[CH:12]2[CH2:17][CH2:16][CH2:15][N:14]([CH3:18])[CH2:13]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1>[C:26]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[CH:12]2[CH2:17][CH2:16][CH2:15][N:14]([CH3:18])[CH2:13]2)=[CH:4][CH:3]=1)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 18967529HCID 18967529, compound2×

Product 1

HCID 18967541HCID 18967541, compoundYield 31.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 7-amino-1-(1-methyl-3-piperidinyl)-naphthalene (0.203 g, 0.845 mmol, product of example 61) and triethylamine (0.141 mL, 1.01 mmol) in tetrahydrofuran (5 mL) was chilled to 0° C. and benzoyl chloride (0.118 mL, 1.01 mmol) was added. The mixture was warmed to room temperature and stirred overnight. The reaction was concentrated at reduced pressure and the residue was taken up in methylene chloride. The organic phase was extracted with 0.5N sodium hydroxide and brine, dried, concentrated onto silica gel and flash chromatographed (1×2 inches). Elution proceeded as follows: 50% ethyl acetate/hexane (225 mL), 75% ethyl acetate/hexane (150 mL) nil; 75% ethyl acetate/hexane (400 mL) and ethyl acetate (200 mL) 0.198 g of pink foam. This product was converted to an HCl salt in methanol, treated with activated carbon, and filtered. The filtrate was concentrated and triturated with ether to give 0.091 g (31%) of the title compound as an amorphous solid with a melting range of 140°-170° C. 1H NMR (DMSO d6) δ 10.59 (s, 1 H), 10.34 (br s, 1 H), 8.73 (s, 1H), 8.06 (d, J=7 Hz, 2 H), 7.94 (distorted t, J=10 Hz, 2 H), 7.82 (d, J=7 Hz, 1H), 7.63-7.53 (m, 3 H), 7.47-7.39 (m, 2 H), 3.78 (br t, J=12 Hz, 1 H), 3.56 (br t, J=11 Hz, 2 H), 3.05 (br s, 1 H), 2.83 (br s, 3 H), 2.15-1.97 (m0 2 H), 1.71 (br s, 1 H). HRMS m/e calculated for C23H24N2O; m/e 344.1883. Observed m/e 344.1886.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. concentrationThe reaction was concentrated at reduced pressure
  3. extractionThe organic phase was extracted with 0.5N sodium hydroxide and brine
  4. customdried
  5. concentrationconcentrated onto silica gel and flash
  6. customchromatographed (1×2 inches)
  7. washElution
  8. additiontreated with activated carbon
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customtriturated with ether

Sources & evidence

ORD record
ord-4de16e0e86c14e0eaf85a49fced94ba3
Source dataset
uspto-grants-1997_01
Patent number
US05597826

Reaction notes

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