Ammonium Chloride → (S)-3-(4-Bromophenyl)-1-(2-methoxypyrimidin-5-yl)-3-o-tolylpropan-1-one

HRID 1618052Notes

Reaction equation

HRID 1618052 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.[Br:15][C:16]1[CH:21]=[CH:20][C:19]([C@@H:22]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH2:23][C:24](N(OC)C)=[O:25])=[CH:18][CH:17]=1.[Cl-].[NH4+]>O1CCCC1>[Br:15][C:16]1[CH:17]=[CH:18][C:19]([C@@H:22]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH2:23][C:24]([C:7]2[CH:8]=[N:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=2)=[O:25])=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 139657Pyrimidine, 5-bromo-2-methoxy-HCID 71813343(S)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamideHCID 178418339Butyllithium

Product 1

HCID 67015720(S)-3-(4-Bromophenyl)-1-(2-methoxypyrimidin-5-yl)-3-o-tolylpropan-1-oneYield 38.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of n-butyllithium (1.6 M in hexane, 3.31 mL, 5.3 mmol) in tetrahydrofuran (12 mL) was cooled to −95° C. and added dropwise, under nitrogen, to a stirred, cooled (−95° C.) solution of 5-bromo-2-methoxypyrimidine (1.00 g, 5.3 mmol) in dry tetrahydrofuran (40 mL). To the resulting yellow solution was immediately added a solution of (S)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamide (example 142, step 1; 1.6 g, 4.42 mmol) in dry THF (12 mL), with the temperature of the reaction mixture being kept between −90° C. and −100° C. The solution was stirred and allowed to warm to room temperature over 2 h. The reaction mixture was poured onto sat. aq. ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) produced the title compound (700 mg, 35%), Colourless gum, MS (ESI+): m/z=: 411.2 [M+H]+.

Workup

  1. additionadded dropwise, under nitrogen, to a stirred
  2. custombeing kept between −90° C. and −100° C
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-be7143772928470d96bb2143f067337c
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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