4-(morpholinomethyl)benzoic acid → 2-(4-Hydroxy-4-phenylpiperidino)-1-(4-(4-(morpholinomethyl)benzoyloxy)phenyl)-1-propanone

HRID 2255995Notes

Reaction equation

HRID 2255995 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.O[C:18]1[CH:23]=[CH:22][C:21]([C:24](=[O:40])[CH:25]([N:27]2[CH2:32][CH2:31][C:30]([OH:39])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:29][CH2:28]2)[CH3:26])=[CH:20][CH:19]=1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[OH:39][C:30]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:31][CH2:32][N:27]([CH:25]([CH3:26])[C:24]([C:21]2[CH:20]=[CH:19][C:18]([O:13][C:12](=[O:14])[C:11]3[CH:15]=[CH:16][C:8]([CH2:7][N:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)=[CH:9][CH:10]=3)=[CH:23][CH:22]=2)=[O:40])[CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 7035074-(morpholinomethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 152803431-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanone

Product 1

HCID 152803442-(4-Hydroxy-4-phenylpiperidino)-1-(4-(4-(morpholinomethyl)benzoyloxy)phenyl)-1-propanoneYield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(morpholinomethyl)benzoic acid (3.17 g, 12.3 mmol), 1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanone (4.0 g, 12.29 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (2.36 g, 12.31 mmol) in methylene chloride (75 mL) was added 4-dimethylaminopyridine (1.88 g, 15.39 mmol). The heterogeneous mixture was allowed to stir overnight under a nitrogen atmosphere at ambient temperature. The mixture was washed with saturated aqueous bicarbonate (2×50 mL), dried by filtration through phase separating filter paper, and concentrated to a glassy yellow solid. Trituration with ether and hexane yielded 5.17 g, 80% of a light yellow solid product which was suitable for further reaction without additional purification. A sample recrystallized from ethyl acetate/hexane had: m.p. 126°-126.5° C.; NMR (CDCl3) 8.22 (d, J=8.6 Hz, 2H), 8.13 (d, J=7.8 Hz, 2H), 7.47 (t, J=7.3 Hz, 4H), 7.34-7.19 (m, 5H), 4.13 (q, J=6.6 Hz, 1H), 3.70 (t, J=4.4 Hz, 4H), 3.57 (s, 2H), 2.97-2.79 (m, 2H), 2.67-2.60 (m, 2H), 2.44 (t, J=4.5 Hz, 4H), 2.18-1.98 (m, 2H), 1.78-1.67 (m, 3H), 1.31 (d, J=6.6 Hz, 3H). IR (KBr) 3270, 2960, 2942, 2912, 2830, 2821, 1743, 1682, 1596, 1390, 1273, 1199.

Workup

  1. washThe mixture was washed with saturated aqueous bicarbonate (2×50 mL)
  2. customdried by filtration through phase
  3. customseparating
  4. filtrationfilter paper
  5. concentrationconcentrated to a glassy yellow solid

Sources & evidence

ORD record
ord-008a20f2050b4645a350fb4b481a86e9
Source dataset
uspto-grants-1997_08
Patent number
US05654302

Reaction notes

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