2,2,6,6-Tetramethylpiperidine → (S)-3-(4-Bromophenyl)-1-(3-methoxypyridazin-4-yl)-3-o-tolylpropan-1-one

HRID 1527972Notes

Reaction equation

HRID 1527972 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[CH3:16][O:17][C:18]1[N:19]=[N:20][CH:21]=[CH:22][CH:23]=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([C@@H:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[CH2:32][C:33](N(OC)C)=[O:34])=[CH:27][CH:26]=1.[Cl-].[NH4+]>C1COCC1>[Br:24][C:25]1[CH:26]=[CH:27][C:28]([C@@H:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[CH2:32][C:33]([C:23]2[CH:22]=[CH:21][N:20]=[N:19][C:18]=2[O:17][CH3:16])=[O:34])=[CH:29][CH:30]=1

Participants

7

Reactant 5

HCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 2924933-MethoxypyridazineHCID 71813343(S)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamideHCID 178418339Butyllithium

Product 1

HCID 86684800(S)-3-(4-Bromophenyl)-1-(3-methoxypyridazin-4-yl)-3-o-tolylpropan-1-oneYield 37.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 2,2,6,6-tetramethylpiperidine (1.28 g, 9.09 mmol) in THF (60 mL) was added n-butyllithium (1.6 M in hexane 6.7 mL, 9.1 mmol) at −30° C., then the solution was stirred at 0° C. for 45 min. After cooling to −70° C. a solution of 3-methoxypyridazine (1.00 g, 9.09 mmol) in THF (6 mL) was added dropwise, then a solution of (S)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamide (example 1, step 5; 823 mg, 2.27 mmol) in THF (6 mL) was added, maintaining the temperature as close as possible to −70° C. The mixture was stirred for 30 min. Sat. aq. ammonium chloride solution (30 mL) was added. The reaction mixture was allowed to reach room temperature and then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) afforded the title compound (349 mg, 37%). Light red solid, MS: 411.1 [M+H]+.

Workup

  1. additionwas added dropwise
  2. temperaturemaintaining the temperature
  3. customas close as possible to −70° C
  4. stirringThe mixture was stirred for 30 min
  5. customto reach room temperature
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-b6af5ab7842a465bbe7a014da83975e8
Source dataset
uspto-grants-2015_07
Patent number
US09090565B2

Reaction notes

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