Triethylamine → HCID 54083497, compound

HRID 399445Notes

Reaction equation

HRID 399445 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15](OS(C(F)(F)F)(=O)=O)[CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.C([N:28]([CH2:31][CH3:32])[CH2:29]C)C.[C:33]1([CH2:39]CCN)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[C]=[O:44]>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:33]1([CH2:39][CH2:32][CH2:31][NH:28][C:29]([C:15]2[CH:16]=[C:17]3[C:12]([CH:11]=[CH:10][CH:9]=[C:8]3[CH:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:13][CH:14]=2)=[O:44])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 162593-PhenylpropylamineHCID 221156371-(1-Methylpiperidin-4-yl)-7-trifluoromethylsulfonyloxynaphthaleneHCID 178418416HCID 178418416, compound

Product 1

HCID 54083497HCID 54083497, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 1-(1-methylpiperidin-4-yl)-7-trifluoromethanesulfonyloxynaphthalene (0.25 g, 0.67 mmol), triethylamine (0.373 mL, 2.68 mmol), 3-phenylpropylamine (0.286 mL, 2.01 mmol), and bis-(triphenylphosphine)palladium chloride (0.025 g, 0.033 mmol) was blanketed with an atmosphere of carbon monoxide (balloon) and heated to 105° C. for 16 h. The reaction was diluted with ethyl acetate and filtered through celite. The filtrate was washed with water and brine, dried and concentrated. The residue was flash chromatographed on silica gel (1×3 inches packed with 75% ethyl acetate/hexane). Elution proceeded as follows: 75% ethyl acetate/hexane, 150 mL, nil; ethyl acetate, 150 mL, nil; 2% methanol/1% triethylamine/ethyl acetate, 200 mL and 2% methanol/1% triethylamine/ethyl acetate, 100 mL, 0.21 g of an oil. Bulb to bulb distillation removed impurities (pot temperature up to 120° C., 1 mm mercury (Hg)). The pot residue was pure product and weighed 0.190 g (73%). The 1-(1-methylpiperidin-4-yl)-7-naphthalene carboxylic acid 3-phenylpropyl amide obtained in this manner solidified on standing and had mp 47°-50° C.; 1H NMR (250 MHz, CDCl3) δ 8.67 (s, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.73 (d, J=6.5 Hz, 1H), 7.61-7.43 (m, 3H), 7.36-7.18 (m, 5H), 6.33 (br s, 1H), 3.58 (q, J=6.5 Hz, 2H), 3.42 (sym m, 1H), 3.05 (br d, J=11.5 Hz, 2H), 2.77 (t, J=7.5 Hz, 2H), 2.38 (s, 3H), 2.27 (sym m, 2H), 2.10-1.88 (m, 6H). Analysis calculated for C26 H30N2O·0.75 H2O: C, 78.06; H, 7.94; N, 7.00. Found: C, 77.92; H, 7.91; N, 6.70.

Workup

  1. filtrationfiltered through celite
  2. washThe filtrate was washed with water and brine
  3. customdried
  4. concentrationconcentrated
  5. customchromatographed on silica gel (1×3 inches packed with 75% ethyl acetate/hexane)
  6. washElution
  7. distillationBulb to bulb distillation
  8. customremoved impurities (pot temperature up to 120° C., 1 mm mercury (Hg))

Sources & evidence

ORD record
ord-7516066d2b0d48c3923edaad0dc990bc
Source dataset
uspto-grants-1998_10
Patent number
US05821245

Reaction notes

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