Ammonium Chloride → HCID 58557210, compound

HRID 1969521Notes

Reaction equation

HRID 1969521 reaction equation
[CH2:1]([Mg]Br)[CH3:2].C(OP(O[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][C:15]=1[C:27]([O:29][CH2:30][CH3:31])=[O:28])(OCC)=O)C.[NH4+].[Cl-]>C1COCC1.[Cu]I>[CH2:1]([C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][C:15]=1[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH3:2]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 58557150HCID 58557150, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 58557210HCID 58557210, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a slurry of CuI (4.21 g, 22.12 mmol) in THF (61.4 mL) at about 0° C. was added ethylmagnesium bromide (1.0 M in THF, 44.2 mL, 44.2 mmol) dropwise. After about 30 min, the reaction mixture was cooled to about −78° C. and a solution of 1-tert-butyl 3-ethyl 4-(diethoxyphosphoryloxy)-5,6-dihydropyridine-1,3(2H)-dicarboxylate (7.51 g, 18.43 mmol) in THF (61 mL) was added slowly. The reaction mixture was stirred at about −78° C. for about 1 h then warmed to about 0° C. The reaction mixture was stirred at about 0° C. for about 1.5 h, then warmed to ambient temperature and stirred for about 1 h. The reaction mixture was cooled to about −78° C. and saturated aqueous NH4Cl (100 mL) was slowly added. The reaction mixture was allowed to warm to ambient temperature and stirred for about 16 h. The mixture was extracted with Et2O (100 mL). The aqueous layer was further extracted with Et2O (2×50 mL). The organic layers were combined, washed with saturated aqueous NH4Cl (50 mL), dried over anhydrous Na2SO4, filtered, concd under reduced pressure and purified by silica gel chromatography eluting with a gradient of 0-30% EtOAc in heptane to yield 1-tert-butyl 3-ethyl 4-ethyl-5,6-dihydropyridine-1,3(2H)-dicarboxylate (0.785 g, 15%) as a clear oil: 1H NMR (CDCl3) δ 4.23 (d, J=7.1 Hz, 2H), 4.12 (s, 2H), 3.48 (t, J=5.8 Hz, 2H), 2.52 (q, J=7.5 Hz, 2H), 2.28 (t, J=5.8 Hz, 2H), 1.51 (s, 9H), 1.32 (t, J=7.1 Hz, 3H), 1.09 (t, J=7.5 Hz, 3H).

Workup

  1. temperaturethen warmed to about 0° C
  2. stirringThe reaction mixture was stirred at about 0° C. for about 1.5 h
  3. temperaturewarmed to ambient temperature
  4. stirringstirred for about 1 h
  5. temperatureThe reaction mixture was cooled to about −78° C.
  6. temperatureto warm to ambient temperature
  7. stirringstirred for about 16 h
  8. extractionThe mixture was extracted with Et2O (100 mL)
  9. extractionThe aqueous layer was further extracted with Et2O (2×50 mL)
  10. washwashed with saturated aqueous NH4Cl (50 mL)
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. custompurified by silica gel chromatography
  14. washeluting with a gradient of 0-30% EtOAc in heptane

Sources & evidence

ORD record
ord-056d5600e15b46a89d7facd9b78c4646
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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