N-Methylbenzamide → HCID 19029150, compound

HRID 2256061Notes

Reaction equation

HRID 2256061 reaction equation
CN[C:3](=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([Li])(C)(C)C.[CH2:16]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCCC1>[CH2:16]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29]2([C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3](=[O:10])[O:32]2)[CH2:28][CH2:27]1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 11954N-MethylbenzamideHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 19029150HCID 19029150, compoundYield 553.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-methylbenzamide (0.38 g) in 200 mL of anhydrous tetrahydrofuran was cooled to -78° C. and treated with tert-butyl lithium (30 mL, 1.7M). At the end of the addition, the reaction mixture was allowed to warm to 0° C. and stirred at this temperature for 1 hour and then cooled back to -78° C. After treatment with a solution of 1-benzyloxycarbonyl-4-piperidone (5.83 g) in 2 mL of tetrahydrofuran, the reaction mixture was stirred at -78° C. for 40 minutes and then quenched with 300 mL of saturated ammonium chloride solution. Extraction with ethyl acetate, washing the organic layer with brine, drying over magnesium sulfate and evaporation afforded the crude product. This material was partially purified by column chromatography; elution with ethyl acetate:hexane (6:4) afforded the named material (5.25 g); MS: 238 (M-99); NMR: 1.6-1.7 (m, 2), 2.0-2.1 (m, 2), 3.4 (br., 2), 4.0-4.1 (br, 2), 5.2(s, 1), 7.2-7.4 (m, 5), 7.5 (m, 1), 7.7 (m, 1), 7.9 (m, 1).

Workup

  1. additionAt the end of the addition
  2. temperaturecooled back to -78° C
  3. customquenched with 300 mL of saturated ammonium chloride solution
  4. extractionExtraction with ethyl acetate
  5. washwashing the organic layer with brine
  6. dry with materialdrying over magnesium sulfate and evaporation
  7. customafforded the crude product
  8. customThis material was partially purified by column chromatography
  9. washelution with ethyl acetate:hexane (6:4)

Sources & evidence

ORD record
ord-8ee6277a46aa49c086e8b536e8ea225e
Source dataset
uspto-grants-1997_08
Patent number
US05654299

Reaction notes

Loading…