Ethyl 4-piperidinecarboxylate → HCID 178469217, compound

HRID 525480Notes

Reaction equation

HRID 525480 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([C:22](=O)[CH3:23])[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH:25]1[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:27][CH2:26]1.[BH3-]C#N.[Na+]>CCO>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH:22]([N:25]2[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:27][CH2:26]2)[CH3:23])[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 5003444Sodium cyanoborohydrideHCID 178466008HCID 178466008, compound

Product 1

HCID 178469217HCID 178469217, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(6-((trans-4-(tert-butyl)cyclohexyl)oxy)naphthalen-2-yl)ethanone (200 mg, 0.62 mmol) and ethyl 4-piperidinecarboxylate (146 mg, 0.93 mmol, 1.5 eq) in anhydrous EtOH (5 mL) was stirred at room temperature for 15 min, then Ti(OEt)4 (356 mg, 1.23 mmol, 2 eq) was added. The reaction mixture was stirred at reflux for 16 h under N2. After cooling to room temperature, the mixture was concentrated and the residue was dissolved in EtOH (3 mL) and NaBH3CN (125 mg, 1.85 mmol, 3 eq) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated and purified by silica gel (PE/EA=4/1) to give ethyl 1-(1-(6-((trans-4-(tert-butyl)cyclohexyl)oxy)naphthalen-2-yl)ethyl)piperidine-4-carboxylate as yellow oil (140 mg, yield: 53%). ESI-MS (M+H+): 466.4. 1H NMR (400 MHz, CDCl3) δ: 7.71-7.65 (m, 2H), 7.60 (s, 1H), 7.44 (d, J=8.0 Hz, 1H), 7.14-7.11 (m, 2H), 4.29-4.24 (m, 1H), 4.11 (q, J=7.2 Hz, 2H), 3.56 (br, 1H), 3.07 (br, 1H), 2.84 (br, 1H), 2.29-2.20 (m, 3H), 2.08-2.01 (m, 4H), 1.90-1.81 (m, 5H), 1.45-1.38 (m, 5H), 1.26-1.09 (m, 6H), 0.89 (s, 9H).

Workup

  1. stirringThe reaction mixture was stirred
  2. temperatureat reflux for 16 h under N2
  3. temperatureAfter cooling to room temperature
  4. concentrationthe mixture was concentrated
  5. dissolutionthe residue was dissolved in EtOH (3 mL)
  6. stirringThe reaction mixture was stirred at room temperature for 2 h
  7. concentrationThe mixture was concentrated
  8. custompurified by silica gel (PE/EA=4/1)

Sources & evidence

ORD record
ord-f968dbadaa644324931c6745a000f1f5
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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