Triethylamine → 3-[4-Benzyl-2-(4-hydroxypiperidino)-5-pyridyl]ethynyl-3-quinuclidinol

HRID 1359395Notes

Reaction equation

HRID 1359395 reaction equation
[CH2:1]([C:8]1[C:13](Br)=[CH:12][N:11]=[C:10]([N:15]2[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]2)[CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([C:24]1([OH:32])[CH:29]2[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]2)[CH2:25]1)#[CH:23].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>[CH2:1]([C:8]1[C:13]([C:23]#[C:22][C:24]2([OH:32])[CH:29]3[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]3)[CH2:25]2)=[CH:12][N:11]=[C:10]([N:15]2[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]2)[CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 181823874-Benzyl-5-bromo-2-(4-hydroxypiperidino)pyridine

Product 1

HCID 181824323-[4-Benzyl-2-(4-hydroxypiperidino)-5-pyridyl]ethynyl-3-quinuclidinolYield 37%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 270 mg of 4-benzyl-5-bromo-2-(4-hydroxypiperidino)pyridine, 130 mg of 3-ethynyl-3-quinuclidinol, 50 mg of tetrakis(triphenylphosphine)palladium(0), 2 mg of cuprous iodide, 0.35 ml of triethylamine and 2 ml of N,N-dimethylformamide was stirred at 100° C. for 3 hours in a nitrogen atmosphere. After cooling as it was, the reaction solution was extracted with ethyl acetate-aqueous dilute ammonia. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated. The residue was subjected to NH-silica gel column chromatography and eluted with 20-100% ethyl acetate/hexane and then with 5% methanol/ethyl acetate, to give 120 mg of the target compound.

Workup

  1. temperatureAfter cooling as it
  2. extractionthe reaction solution was extracted with ethyl acetate-aqueous dilute ammonia
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated
  6. washeluted with 20-100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-b5a63aca81b64fe799b1f1f1545150a5
Source dataset
uspto-grants-2003_07
Patent number
US06599917B1

Reaction notes

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