4-Methylmorpholine → Ammonium Hydroxide

HRID 2259230Notes

Reaction equation

HRID 2259230 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH:10]=[C:9]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[CH2:8][CH2:7]1.Cl[C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][N:24]=1.CN1CC[O:34]CC1>C(Cl)(Cl)Cl>[NH4+:2].[OH-:34].[CH3:1][N:2]([C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][N:24]=1)[CH2:3][CH2:4][CH2:5][N:6]1[CH2:7][CH:8]=[C:9]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[CH2:10][CH2:11]1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 335152,4-DichloropyridineHCID 19002983HCID 19002983, compound

Product 2

HCID 14923Ammonium HydroxideHCID 15295391HCID 15295391, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

3,6-Dihydro-N-methyl-4-(1-naphthalenyl)-1-(2H)-pyridinepropanamine (2.05 g, 7.30 mmol), 2,4-dichloropyridine (1.08 g, 7.30 mmol), and 4-methylmorpholine (10 mL) were heated in a Parr bomb at 140° C. for 72 h. Upon cooling to room temperature the crude mixture was diluted with chloroform (700 mL) and washed with 100 mL portions of aqueous 10% potassium carbonate and saturated aqueous sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Silica gel chromatography (50:50:1 toluene:EtOAc:NH4OH) of the concentrate afforded 3,6-dihydro-N-methyl-N-(4-chloro-2-pyridinyl)-4-(1- naphthalenyl)-1(2H)-pyridinepropanamine (A) (244 mg) and 3,6-dihydro-N-methyl-N-(2-chloro-4-pyridinyl)-4-(1-naphthalenyl)-1(2H)-pyridinepropanamine B) (190 mg). The fumarate salts were made by dissolving the free bases (232 mg (A), 0.59 mmol; 200 mg (B), 0.51 mmol) along with fumaric (137 mg, 1.18 mmol; 188 mg, 1.02 mmol respectively) in a solution of hot EtOAc (10 mL) followed by the addition of minimal amounts of MeOH. Upon cooling to room temperature overnight the resultant crystals (128 mg, 41% yield of A; 148 mg, 56% yield of B) were collected by filtration and dried at 65° C. under vacuum (0.05 mm Hg) for 20 h.

Workup

  1. washwashed with 100 mL portions of aqueous 10% potassium carbonate and saturated aqueous sodium chloride
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-2e9b8ce457094881b5a7b70a99d3bb5e
Source dataset
uspto-grants-1995_12
Patent number
US05472966

Reaction notes

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