Triethylamine → N,N-Dimethyl-4-[5-fluoro-3-[4-(2-methylimidazol-1-yl)benzyloxy]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide

HRID 1418459Notes

Reaction equation

HRID 1418459 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH:29]=[CH:28][N:27]=[C:26]3[CH3:30])=[CH:21][CH:20]=2)[CH:5]=[C:6]([C:8]2([C:14](O)=[O:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.Cl.[CH3:32][NH:33][CH3:34].C(N(CC)CC)C.C(P(=O)(OCC)OCC)#N>C1COCC1.O>[CH3:32][N:33]([CH3:34])[C:14]([C:8]1([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[C:4]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([N:25]4[CH:29]=[CH:28][N:27]=[C:26]4[CH3:30])=[CH:23][CH:24]=3)[CH:5]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)=[O:15]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 76257Diethyl cyanophosphonateHCID 113158374-(3-Fluoro-5-((4-(2-methyl-1H-imidazol-1-YL)benzyl)oxy)phenyl)tetrahydro-2H-pyran-4-carboxylic acid

Product 1

HCID 11774961N,N-Dimethyl-4-[5-fluoro-3-[4-(2-methylimidazol-1-yl)benzyloxy]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxamideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 4-[5-fluoro-3-[4-(2-methylimidazol-1-yl)benzyloxy]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxylic acid (100 mg, 0.24 mmol), dimethylamine hydrochloride (98 mg, 1.2 mmol) and triethylamine (253 mg, 2.5 mmol) in THF (50 ml) at 0° C. was added diethyl cyanophosphonate (44 mg, 0.27 mmol). After 10 min, the reaction was diluted with water (50 ml) and extracted with ethyl acetate (50 ml). The extract was washed with water (50 ml) and brine (50 ml), dried over magnesium sulfate and concentrated. Purification of the residue was performed by column chromatography (silica-gel, 50 g; gradient polarity of eluant from dichloromethane to 5% methanol in dichloromethane) to give 117 mg of crude product as a colorless foam. Recrystallization from a mixture of isopropyl ether-ethyl acetate (1:1) to give the titled compound (51 mg, 50%).

Workup

  1. extractionextracted with ethyl acetate (50 ml)
  2. washThe extract was washed with water (50 ml) and brine (50 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customPurification of the residue
  6. customto give 117 mg of crude product as a colorless foam
  7. customRecrystallization
  8. additionfrom a mixture of isopropyl ether-ethyl acetate (1:1)

Sources & evidence

ORD record
ord-f9ad84d8f6b3448bb0786881c60c5a41
Source dataset
uspto-grants-1999_03
Patent number
US05883106

Reaction notes

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