Phenylacetylene → HCID 69093897, compound

HRID 2362466Notes

Reaction equation

HRID 2362466 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[O:11][C:10](=[O:20])[NH:9]2)[CH:5]=[N:6][CH:7]=1.F[C:22]1[CH:27]=[CH:26][C:25](F)=[CH:24][C:23]=1[C@H:29]1[O:33]C(=O)N[C@@H:30]1[C:35]1[CH:36]=[N:37][CH:38]=[C:39](C#C)C=1.FC1C=CC=CC=1C=O.C(C1C=CC=CC=1)#C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(N(CC)CC)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[C:12]([O-:11])(=[O:33])[CH3:13].[NH4+:6].[CH2:36]([NH:37][CH2:38][CH3:39])[CH3:35].[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C@H:12]1[O:11][C:10](=[O:20])[NH:9][C@@H:8]1[C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:30]#[C:29][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:22]=2)[CH:3]=1

Participants

11

Reactant 5

HCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 67970o-FluorobenzaldehydeHCID 69282126HCID 69282126, compoundHCID 86673452HCID 86673452, compound

Product 3

HCID 8021DiethylamineYield 0.1%HCID 517165Ammonium AcetateHCID 69093897HCID 69093897, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Procedure

To a slurry of (4R,5R)-4-(5-bromopyridin-3-yl)-5-(2-fluorophenyl)oxazolidin-2-one (100 mg, 0.297 mmol; prepared in analogous fashion to the preparation of (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one starting from 2-fluorobenzaldehyde in place of 2,5-difluorobenzaldehyde) in triethylamine (Volume: 5 mL) was bubbled nitrogen for 20 min. Ethynylbenzene (0.049 mL, 0.445 mmol) was added and nitrogen bubbling was continued for 5 min before adding bis(triphenylphosphine) palladium (II) chloride (15.61 mg, 0.022 mmol), triphenylphosphine (14.00 mg, 0.053 mmol), and copper (I) iodide (4.24 mg, 0.022 mmol) in 1 portion. After 5 min of additional nitrogen bubbling, the vessel was placed in a 70° C. bath under nitrogen for 18 h at which time it was cooled and concentrated. The residue was dissolved in methanol and purified via preparative liquid chromatography (Sunfire C18 OBD 30×100 mm 5 μm, A=95% H2O/5% Acetonitrile, B=95% Acetonitrile/5% H2O, Modifier 10 mM Ammonium Acetate, 0.00 min=20% B, 8.0 min=100% B, 13.0 min=100% B, Flow rate=40 mL/min) and then by chiral HPLC (Chiralpak AD 21×250 10 μm, A=Heptane with 0.1% diethylamine, B=Ethanol, Isocratic 50% A, Flow Rate=15 mL/min providing (4R,5R)-5-(2-fluorophenyl)-4-(5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one (61 mg; 57%). 1H NMR (500 MHz, CDCl3) δ ppm 8.78 (1H, d, J=1.83 Hz), 8.48 (1H, d, J=1.83 Hz), 7.92 (1H, t, J=1.98 Hz), 7.56 (2H, dd, J=6.71, 2.75 Hz), 7.46-7.53 (1H, m), 7.34-7.46 (4H, m), 7.20-7.31 (1H, m), 7.06-7.20 (1H, m), 5.58 (1H, d, J=5.80 Hz), 5.44 (1H, br. s.), 4.86 (1H, d, J=5.80 Hz). Mass Spectral Anal. Calcd. for [M+H]+ C22H15FN2O2: 359.1. found 359.1.

Workup

  1. customwas bubbled nitrogen for 20 min
  2. waitAfter 5 min of additional nitrogen bubbling
  3. customwas placed in a 70° C.
  4. customfor 18 h
  5. temperaturewas cooled
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in methanol
  8. custompurified via preparative liquid chromatography (Sunfire C18 OBD 30×100 mm 5 μm

Sources & evidence

ORD record
ord-69c2a7a391c944638da737d9b6b64423
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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