4-Vinylpyridine → N-Boc-(R)-2-(3-(2-(4-pyridinyl)vinyl)-benzyl)morpholine

HRID 2252990Notes

Reaction equation

HRID 2252990 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21]O)[CH:16]=2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([N:30]1[CH2:35][CH2:34]O[C@H:32]([CH2:36][C:37]2C=CC=C(Br)C=2)[CH2:31]1)(OC(C)(C)C)=O.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(C1C=CN=CC=1)=C.C(N(CC)CC)C>CC#N.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]=[CH:37][C:36]3[CH:32]=[CH:31][N:30]=[CH:35][CH:34]=3)[CH:16]=2)[CH2:9]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

8

Reactant 5

HCID 75024-VinylpyridineHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 67073062N-Boc-(R)-2-(3-(hydroxymethyl)benzyl)morpholineHCID 67073309N-Boc-(R)-2-(3-bromobenzyl)morpholine

Product 1

HCID 67073377N-Boc-(R)-2-(3-(2-(4-pyridinyl)vinyl)-benzyl)morpholineYield 57%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

Intermediate (b) N-Boc-(R)-2-(3-bromobenzyl)morpholine (103 mg, 0.29 mmol), was dissolved in CH3CN (2 mL) with palladium acetate (3.2 mg, 14 umol), tris(ortho-tolyl)phosphine (8.8 mg, 29 umol), 4-vinylpyridine (61 mg, 0.58 mmol) and triethyl amine (58 mg, 0.58 mmol). The reaction was then subjected to microwave heating at 140° C. for 5 minutes. The reaction was cooled to room temperature, partitioned between ethyl acetate (20 mL) and water (20 mL) and separated. The organic layer was washed with brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica; 20-30% ethyl acetate/isohexane) to yield the desired intermediate (a), N-Boc-(R)-2-(3-(2-(4-pyridinyl)vinyl)-benzyl)morpholine as a colorless gum (63 mg, 57%).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. custompartitioned between ethyl acetate (20 mL) and water (20 mL)
  3. customseparated
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (silica; 20-30% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-6f0aa0debdd94eefa1094fae778462a7
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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