3-Bromopyridine → N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholine

HRID 2253001Notes

Reaction equation

HRID 2253001 reaction equation
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1.C(N1CCO[C@H](CC2C=CC=C(CO)C=2)C1)(OC(C)(C)C)=O.[C:52]([N:59]1[CH2:64][CH2:63][O:62][C@H:61]([CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([CH:72]=[CH2:73])[CH:67]=2)[CH2:60]1)([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:52]([N:59]1[CH2:64][CH2:63][O:62][C@H:61]([CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([CH:72]=[CH:73][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[CH:67]=2)[CH2:60]1)([O:54][C:55]([CH3:56])([CH3:58])[CH3:57])=[O:53]

Participants

7

Reactant 4

HCID 122863-BromopyridineHCID 80271Tri-o-tolylphosphineHCID 67073044N-Boc-(R)-2-(3-vinylbenzyl)morpholineHCID 67073062N-Boc-(R)-2-(3-(hydroxymethyl)benzyl)morpholine

Product 1

HCID 67073511N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholineYield 60.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To a small reaction vessel was added palladium acetate (1.5 mg, 7micromol), tris-(ortho-toluyl)phospine (4.2 mg, 14micromol) and 3-bromopyridine (22 mg, 0.13 mmol) as a solution in acetonitrile (1.5 mL) in one portion. The mixture was stirred for 5 minutes at room temperature under an atmosphere of nitrogen gas and then intermediate (b), N-Boc-(R)-2-(3-vinylbenzyl)morpholine (0.083 g, 0.27 mmol) was added as a solution in acetonitrile (1.5 mL). The reaction vessel was then subjected to microwave power to heat the reaction to 140° C. for 5 minutes and then cooled to room temperature. The crude reaction was added directly to a silica column and the mixture washed with solvent (10-60% ethyl acetate:isohexane). The desired material was concentrated in vacuo and purified by column chromatography (silica; 50% ethyl acetate: isohexane) to obtain the desired coupling product intermediate (a), N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholine as a colorless oil (30 mg, 57%).

Workup

  1. temperatureto heat
  2. customthe reaction to 140° C. for 5 minutes
  3. temperaturecooled to room temperature
  4. customThe crude reaction
  5. additionwas added directly to a silica column
  6. washthe mixture washed with solvent (10-60% ethyl acetate:isohexane)
  7. concentrationThe desired material was concentrated in vacuo
  8. custompurified by column chromatography (silica; 50% ethyl acetate: isohexane)

Sources & evidence

ORD record
ord-4d6e9a96107f4720b232d94df7050a04
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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