Triethylamine → HCID 18182214, compound

HRID 1359338Notes

Reaction equation

HRID 1359338 reaction equation
[C:1]1([C:7]2[C:12](I)=[CH:11][CH:10]=[C:9]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20]([C:22]1([OH:30])[CH:27]2[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]2)[CH2:23]1)#[CH:21].C(N(CC)CC)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C)C=O>[C:1]1([C:7]2[C:12]([C:21]#[C:20][C:22]3([OH:30])[CH:27]4[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]4)[CH2:23]3)=[CH:11][CH:10]=[C:9]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 18182331HCID 18182331, compound

Product 1

HCID 18182214HCID 18182214, compoundYield 55.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 500 mg of 2-phenyl-6-morpholino-3-iodopyridine, 230 mg of 3-ethynyl-3-quinuclidinol, 79 mg of tetrakis(triphenylphosphine)palladium(0), 1.3 mg of cuprous iodide, 0.57 ml of triethylamine and 1 ml of N,N-dimethylformamide was heated under stirring for 4 hours in an oil bath kept at 75° C. in a nitrogen atmosphere. The mixture was extracted by adding aqueous dilute ammonia and ethyl acetate thereto, and the organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to NH-silica gel column chromatography, and eluted with 50% ethyl acetate/hexane, ethyl acetate and then 2.5% methanol/ethyl acetate, and crystallized from ethyl acetate, to give 296 mg of the target compound.

Workup

  1. temperaturewas heated
  2. customkept at 75° C. in a nitrogen atmosphere
  3. extractionThe mixture was extracted
  4. additionby adding aqueous dilute ammonia and ethyl acetate
  5. washthe organic phase was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. washeluted with 50% ethyl acetate/hexane, ethyl acetate
  9. custom2.5% methanol/ethyl acetate, and crystallized from ethyl acetate

Sources & evidence

ORD record
ord-0f845f41b67b4d048b1260a6640f509e
Source dataset
uspto-grants-2003_07
Patent number
US06599917B1

Reaction notes

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