Triethylamine → (4R,5R)-5-Phenyl-4-(2-(pyridin-2-ylethynyl)pyridin-4-yl)oxazolidin-2-one

HRID 2362443Notes

Reaction equation

HRID 2362443 reaction equation
Br[C:2]1[CH:7]=[C:6]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:11][C:10](=[O:19])[NH:9]2)[CH:5]=[CH:4][N:3]=1.C[Si]([C:24]#[C:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C)C=O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:13]1([C@H:12]2[O:11][C:10](=[O:19])[NH:9][C@@H:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:24]#[C:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[CH:7]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 5228592-(Trimethylsilylethynyl)pyridineHCID 2724141Tetrabutylammonium FluorideHCID 86673413(4R,5R)-4-(2-Bromopyridin-4-yl)-5-phenyloxazolidin-2-one

Product 1

HCID 69084771(4R,5R)-5-Phenyl-4-(2-(pyridin-2-ylethynyl)pyridin-4-yl)oxazolidin-2-one

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4R,5R)-4-(2-bromopyridin-4-yl)-5-phenyloxazolidin-2-one (20 mg, 0.063 mmol) and 2-((trimethylsilyl)ethynyl)pyridine (10.99 mg, 0.063 mmol) in dimethylformamide (300 mL) was purged with nitrogen for 30 min. The reaction was treated with triphenylphosphine (4.93 mg, 0.019 mmol), and purged 10 minutes longer. To this was added PdCl2(PPh3)2 (2.199 mg, 3.13 mmol) and copper(I) iodide (1.193 mg, 6.27 mmol). After purging 10 min longer, the reaction was treated with triethylamine (13.1 mL, 0.094 mmol) and placed in an 85° C. oil bath. To this was added tetrabutylammonium fluoride (1M in tetrahydrofuran, 68.9 mL, 0.069 mmol) dropwise. The reaction was stirred at this temperature for 1 h. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (50%-->100% EtOAc/Hex) gave 19 mg (89%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.68 (d, J=4.6, 1H), 8.60 (d, J=5.2, 1H), 7.73 (ddd, J=7.9, 7.6, 1.6, 1H), 7.59 (d, J=7.6, 1H), 7.38-7.50 (m, 5H), 7.33 (m, 3H), 7.25 (m, 1H), 5.19 (d, J=7.3, 1H), 4.88 (d, J=7.3, 1H). 13C-NMR (CDCl3, 126 MHz) δ 158.8, 151.0, 150.3, 148.6, 143.3, 142.1, 136.7, 136.6, 129.6, 129.3, 127.9, 126.2, 125.1, 123.9, 120.9, 88.5, 87.4, 85.2, 63.6. Mass spec.: 342.0 (MH)+.

Workup

  1. custompurged 10 minutes longer
  2. customAfter purging 10 min longer
  3. customplaced in an 85° C.
  4. washwashed with water
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (50%-->100% EtOAc/Hex) gave 19 mg (89%) as a foam solid

Sources & evidence

ORD record
ord-d4ce31934bce4655aad72bda7faddebd
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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