1,2-Dichloroethane → Ethyl 4-[3-hydroxy-3-(4-naphth-2-yl-phenyl)piperidin-1-ylcarbonyl]-3-hydroxy-3-ethoxycarbonylbutanoate

HRID 743724Notes

Reaction equation

HRID 743724 reaction equation
[OH:1][C:2]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=3)=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1.[OH:24][C:25]([C:36]([O:38][CH2:39][CH3:40])=[O:37])([CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:26][C:27](O)=[O:28].C(Cl)CCl.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[OH:1][C:2]1([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=3)=[CH:12][CH:13]=2)[CH2:7][CH2:6][CH2:5][N:4]([C:27]([CH2:26][C:25]([OH:24])([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:28])[CH2:3]1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 153840823-Hydroxy-3-(4-naphth-2-ylphenyl)piperidineHCID 15384083Diethyl Citrate

Product 1

HCID 19424723Ethyl 4-[3-hydroxy-3-(4-naphth-2-yl-phenyl)piperidin-1-ylcarbonyl]-3-hydroxy-3-ethoxycarbonylbutanoateYield 75%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Hydroxy-3-(4-naphth-2-ylphenyl)piperidine (Preparation 7, 1.24 g, 4.09 mmol), 3-hydroxy-3, 4-bis(ethoxycarbonyl)butanoic acid (Preparation 1, 1.01 g, 4.09 mmol), EDC, (0.785 g, 4.09 mmol), 1-hydroxybenzotriazole (HOBT, 0.055 g, 2.05 mmol) and triethylamine (570 μL, 8.18 mmol) in THF or methylene chloride (150 mL) is stirred under argon overnight. The reaction mixture is diluted with CH2Cl2 or ethyl acetate and washed with water or 5% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The organic layer is then dried over MgSO4 or Na2SO4, filtered and concentrated. The crude product is purified by flash chromatography (using 60% ethyl acetate in hexane in this instance) to yield the diester intermediate, ethyl 4-[3-hydroxy-3-(4-naphth-2-yl-phenyl)piperidin-1-ylcarbonyl]-3-hydroxy-3-ethoxycarbonylbutanoate (1.63 g, 75%) as a foam solid.

Workup

  1. washwashed with water or 5% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and brine
  2. dry with materialThe organic layer is then dried over MgSO4 or Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified by flash chromatography (

Sources & evidence

ORD record
ord-58c7fc289bf8439abe9dc5d3302e1145
Source dataset
uspto-grants-1996_09
Patent number
US05556990

Reaction notes

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