Ammonium Chloride → HCID 66821477, compound

HRID 241010Notes

Reaction equation

HRID 241010 reaction equation
[CH3:1][CH:2]1[CH2:7][C:6](=[O:8])[CH:5]=[CH:4][N:3]1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH:33]=[O:34].[Cl-].[NH4+]>C1COCC1>[F:29][C:30]1[CH:31]=[C:32]([CH:33]([OH:34])[CH:7]2[C:6](=[O:8])[CH:5]=[CH:4][N:3]([C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:10])[CH:2]2[CH3:1])[CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 680093-FluorobenzaldehydeHCID 2733832Lithium HexamethyldisilazideHCID 11459227Benzyl 2-methyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 66821477HCID 66821477, compoundYield 66.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of phenylmethyl 2-methyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate (J. Bioorg. Med. Chem. 2007, 1106-1116) (2.4 g, 9.78 mmol) in THF (35 mL) was added dropwise a 1M solution of lithium bis(trimethylsilyl)amide in THF (11 mL) at −78° C. The solution was warmed up to 0° C., stirred at this temperature for 1 h, then cooled again to −78° C. 3-Fluorobenzaldehyde (1.3 mL, 12.7 mmol) was added in one portion. The reaction was stirred for 4 h while allowing it to slowly warm up to 0° C. Then, saturated ammonium chloride (20 mL) was added, and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×20 mL) and the combined organic layers were washed with saturated sodium chloride (50 mL), dried over sodium sulfate, filtered and concentrated. Column chromatography on silica (gradient 20 to 100% ethyl acetate in hexanes) afforded phenylmethyl 3-[(3-fluorophenyl)(hydroxy)methyl]-2-methyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate (2.4 g, 66% yield) as mixture of diastereomers. MS (EI) for C21H20FNO4: 370.1 (MH+).

Workup

  1. temperaturecooled again to −78° C
  2. stirringThe reaction was stirred for 4 h
  3. temperatureto slowly warm up to 0° C
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  6. washthe combined organic layers were washed with saturated sodium chloride (50 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-91f812ae6c6f410a9a20de29f9f2236f
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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