Ammonia → (3R)-3-[2-Benzyl-6-[(3R,4S)-3-hydroxy-4-fluoropyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol

HRID 1359346Notes

Reaction equation

HRID 1359346 reaction equation
[CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@H:18]([F:20])[C@H:17]([OH:21])[CH2:16]2)[N: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.N>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][CH:11]=[C:10]([N:15]2[CH2:19][C@H:18]([F:20])[C@H:17]([OH:21])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 946095(3R)-3-ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 697586992-benzyl-6-[(3R,4S)-3-hydroxy-4-fluoropyrrolidine-1-yl]-3-iodopyridine

Product 1

HCID 59077778(3R)-3-[2-Benzyl-6-[(3R,4S)-3-hydroxy-4-fluoropyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinolYield 69.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 50 mg of 2-benzyl-6-[(3R,4S)-3-hydroxy-4-fluoropyrrolidine-1-yl]-3-iodopyridine, 21 mg of (3R)-3-ethynyl-3-quinuclidinol, 15 mg of tetrakis(triphenylphosphine)palladium(0), 1 mg of cuprous iodide, 53 μl of triethylamine and 3.0 ml of N,N-dimethylformamide was heated under stirring for 3 hours at 75° C. in a nitrogen atmosphere. The reaction solution was poured into an aqueous dilute ammonia, was then extracted with ethyl acetate. Then, the organic phase was washed with brine and the solvent was removed. The residue was subjected to NH-silica gel (Fuji Silicia) column chromatography and eluted with hexane/ethyl acetate (1:1) and then with ethyl acetate/methanol (15:1), to give 37 mg of the target compound.

Workup

  1. temperaturewas heated
  2. extractionwas then extracted with ethyl acetate
  3. washThen, the organic phase was washed with brine
  4. customthe solvent was removed
  5. washeluted with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-e343792b78464cc29e833b8220f66545
Source dataset
uspto-grants-2003_07
Patent number
US06599917B1

Reaction notes

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