Triphenylphosphine → HCID 69085829, compound

HRID 2362465Notes

Reaction equation

HRID 2362465 reaction equation
C(C1C=C([C@@H]2[C@@H:13]([C:14]3C=CC=C(F)C=3)[O:12]C(=O)N2)C=[N:7]C=1)#C.F[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[C@H:30]1[O:34][C:33](=[O:35])[NH:32][C@@H:31]1[C:36]1[CH:37]=[N:38][CH:39]=[C:40]([C:42]#[CH:43])[CH:41]=1.FC1C=C(C=CC=1)C=O.Br[C:54]1[CH:59]=[N:58][CH:57]=[CH:56][N:55]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(C(C)C)CC)(C)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.CN(C)C=O>[C:13]([O-:12])(=[O:34])[CH3:14].[NH4+:7].[F:29][C:26]1[CH:25]=[C:24]([C@H:30]2[O:34][C:33](=[O:35])[NH:32][C@@H:31]2[C:36]2[CH:37]=[N:38][CH:39]=[C:40]([C:42]#[C:43][C:54]3[CH:59]=[N:58][CH:57]=[CH:56][N:55]=3)[CH:41]=2)[CH:23]=[CH:28][CH:27]=1

Participants

11

Reactant 6

HCID 11776TriphenylphosphineHCID 680093-FluorobenzaldehydeHCID 81531DiisopropylethylamineHCID 6428002-BromopyrazineHCID 86673452HCID 86673452, compoundHCID 86673456HCID 86673456, compound

Product 2

HCID 517165Ammonium AcetateHCID 69085829HCID 69085829, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

(4R,5R)-4-(5-ethynylpyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (50 mg, 0.177 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 3-fluorobenzaldehyde in place of 2,5-difluorobenzaldehyde), 2-bromopyrazine (31.0 mg, 0.195 mmol), bis(triphenylphosphine) palladium (II) chloride (6.22 mg, 8.86 mmol), triphenylphosphine (9.29 mg, 0.035 mmol), and copper (I) iodide (1.687 mg, 8.86 mmol) were combined in a microwave vial. Dimethylformamide (0.250 mL) and diisopropylethylamine (0.75 mL) were added resulting in a biphasic mixture. Nitrogen was bubbled through the vessel for 10 min, the vessel was capped and the reaction was run at 120° C. for 25 min on a Biotage microwave reactor. The diisopropylethylamine removed in vacuo, the remaining solution was diluted with methanol and the solution was purified via preparative liquid chromatography (Sunfire C18 19×100 mm 5 nm, 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=25 mL/min) providing (4R,5R)-5-(3-fluorophenyl)-4-(5-(pyrazin-2-ylethynyl)pyridin-3-yl)oxazolidin-2-one (31 mg; 48%) as an amber foam. 1H NMR (500 MHz, CDCl3) δ ppm 8.89 (1H, br. s.), 8.81 (1H, s), 8.63 (1H, d, J=1.53 Hz), 8.57 (1H, d, J=2.44 Hz), 8.52 (1H, br. s.), 7.97 (1H, s), 7.41 (1H, td, J=7.93, 5.49 Hz), 6.94-7.19 (3H, m), 5.61 (1H, br. s.), 5.30 (1H, d, J=7.32 Hz), 4.81 (1H, d, J=7.32 Hz), Mass Spectral Anal. Calcd. for [M+H]+ C20H13FN4O2: 361.1. found 361.2.

Workup

  1. customresulting in a biphasic mixture
  2. customNitrogen was bubbled through the vessel for 10 min
  3. customthe vessel was capped
  4. customThe diisopropylethylamine removed in vacuo
  5. additionthe remaining solution was diluted with methanol
  6. customthe solution was purified via preparative liquid chromatography (Sunfire

Sources & evidence

ORD record
ord-79c27586112c409a8d4cbbeed72848f5
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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