1-Methyl-4-piperidone → HCID 10584532, compound

HRID 1632113Notes

Reaction equation

HRID 1632113 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5](=[O:8])[CH2:4][CH2:3]1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([Mg]Br)=[CH:12][CH:11]=1>C(OCC)C.C(OCC)(=O)C.[Cl-].[NH4+]>[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:5]2([OH:8])[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:12][CH:11]=1

Participants

6

Reactant 2

HCID 740491-Methyl-4-piperidoneHCID 178418676HCID 178418676, compound

Product 1

HCID 10584532HCID 10584532, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-methyl-piperidin-4-one (1.50 g, 13.3 mmol) in diethyl ether (10 mL) was degassed under a nitrogen stream. The solution was cooled to 0° C. in an salt ice bath. To the stirring solution was added 4-fluorophenylmagnesium bromide (1.74 g, 14.6 mmol) dropwise over 5 min. A solid formed partway through the addition, and additional diethyl ether was added (2 mL). The reaction was then stirred at 0° C. for 2 h. To the suspension was added aqueous ammonium chloride (15 mL). The biphasic solution was diluted with ethyl acetate (40 mL) and additional saturated aqueous ammonium chloride (20 mL). The layer was separated, and the organic extract washed with brine (50 mL), dried over sodium sulfate, filtered, and the solvent removed under vacuum to give I-293 (965 mg, 32% yield) as a brown powder. The product was taken on without further purification. 1H NMR (400 MHz, DMSO-d6): 7.51-7.48 (m, 2H), 7.13-7.09 (m, 2H), 4.80 (s, 1H), 2.52-2.53 (m, 3H), 2.36-2.30 (m, 2H), 2.19 (s, 3H), 1.94-1.87 (m, 2H), 1.57-1.54 (m, 2H) ppm.

Workup

  1. customA solid formed partway
  2. additionwas added (2 mL)
  3. customThe layer was separated
  4. extractionthe organic extract
  5. washwashed with brine (50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent removed under vacuum
  9. customto give I-293 (965 mg, 32% yield) as a brown powder
  10. customThe product was taken on without further purification

Sources & evidence

ORD record
ord-53c758ab108048c1917b8fba3c347773
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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