Phenylacetylene → HCID 69081723, compound

HRID 2362449Notes

Reaction equation

HRID 2362449 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:8]2[C@H:12]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[O:11][C:10](=[O:19])[NH:9]2)[CH:5]=[CH:6][CH:7]=1.[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)#[CH:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(N(CC)CC)C.[Cu]I.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>[C:22]1([C:20]#[C:21][C:2]2[CH:3]=[C:4]([C@H:8]3[C@H:12]([C:13]4[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=4)[O:11][C:10](=[O:19])[NH:9]3)[CH:5]=[CH:6][CH:7]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 69082187HCID 69082187, compound

Product 1

HCID 69081723HCID 69081723, compoundYield 29.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

To trans-4-(3-bromophenyl)-5-(pyridin-3-yl)oxazolidin-2-one (46 mg, 0.144 mmol) slurried in triethylamine (3 mL) was added ethynylbenzene (0.021 mL, 0.187 mmol), copper(I) iodide (2.74 mg, 0.014 mmol), and triphenylphosphine (26.5 mg, 0.101 mmol). The reaction mixture was cooled to −78° C. under nitrogen and subjected to three rounds of pump/nitrogen purge. The mixture was then warmed to ambient temperature and (Ph3P)2PdCl2 (10.12 mg, 0.014 mmol) was added. The vessel was fitted with a reflux condensor and placed in an oil bath at 93° C. for 18 h at which time the vessel was removed from the heat and the residue was solubilized in 1:1 dimethylformamide/methanol and purified via preparative HPLC method 4. Pooling and concentration of the fractions containing the peak eluting at 7.37 min provided 14.3 mg trans-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one as an indeterminate enantiomeric mixture. 1H NMR (500 MHz, MeOD) δ ppm 8.44 (1H, d, J=7.32 Hz), 8.16 (1H, br. s.), 7.57-7.63 (2H, m), 7.47-7.57 (4H, m), 7.44 (1H, d, J=7.63 Hz), 7.36-7.42 (4H, m), 5.68 (1H, d, J=6.41 Hz), 4.98 (1H, d, J=6.71 Hz). LC/MS (Analytical HPLC Method 6) 1.97 min, Anal. Calcd. for [M+H]+ C22H16N2O2: 341.12. found 341.29. HPLC retention time (Analytical HPLC method 3): 7.30 min. Further purification via preparative SFC method 5 provided 2.2 mg (4%) (4R,5R)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one (5.8 min retention time) as a colorless oil and 2.0 mg (4%) (4S,5S)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one as a colorless oil. HPLC retention time for (4R,5R)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one (Analytical HPLC method 3): 7.12 min. HPLC retention time for (4S,5S)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one (Analytical HPLC method 3): 7.10 min.

Workup

  1. custompurge
  2. temperatureThe mixture was then warmed to ambient temperature
  3. customThe vessel was fitted with a reflux condensor
  4. customthe vessel was removed from the
  5. temperatureheat
  6. custompurified via preparative HPLC method 4
  7. additionPooling and concentration of the fractions containing the
  8. washpeak eluting at 7.37 min

Sources & evidence

ORD record
ord-5ef948ab583740f39c32fe27d666a1fa
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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