1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-{2-[4-(4-Chlorophenoxy)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one

HRID 1667201Notes

Reaction equation

HRID 1667201 reaction equation
[O:1]=[C:2]1[C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:20][C:21]([OH:23])=O.[Cl:24][C:25]1[CH:37]=[CH:36][C:28]([O:29][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:27][CH:26]=1.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:24][C:25]1[CH:37]=[CH:36][C:28]([O:29][CH:30]2[CH2:31][CH2:32][N:33]([C:21](=[O:23])[CH2:20][N:3]3[CH2:4][CH2:5][CH2:6][C:7]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2]3=[O:1])[CH2:34][CH2:35]2)=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 51998894-(4-Chlorophenoxy)piperidineHCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acid

Product 1

HCID 673576311-{2-[4-(4-Chlorophenoxy)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the product of Example 68E (117 mg, 0.38 mmol), 4-(4-chlorophenoxy)piperidine (80.0 mg, 0.378 mmol), and 4-(dimethylamino)pyridine (4.6 mg, 0.038 mmol) in CH2Cl2 (2 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.067 mL, 0.378 mmol) via syringe. The reaction was stirred at ambient temperature for 45 hours. The reaction mixture was diluted with 50 mL CH2Cl2, then washed with 1 N aqueous HCl, saturated aqueous NaHCO3 solution and brine, dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 50% ethyl acetate/hexanes) which yielded the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.36-7.17 (m, 12H), 6.86-6.80 (m, 2H), 4.55-4.45 (m, 1H), 4.40 (d, J=15.6, 1H), 4.09 (d, J=15.6, 1H), 3.80-3.33 (m, 6H), 2.72-2.57 (m, 2H), 2.00-1.74 (m, 6H); MS (ESI+) m/z 503 (M+H)+.

Workup

  1. washwashed with 1 N aqueous HCl, saturated aqueous NaHCO3 solution and brine
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 50% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-7ea175e41fdd4779a62a2306c75bd507
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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