Dimethylformamide → HCID 69085234, compound

HRID 2362467Notes

Reaction equation

HRID 2362467 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)[O:11][C:10](=[O:20])[NH:9]2)=[CH:4][CH:3]=1.[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)#[CH:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(C(C)C)CC)(C)C.CN(C)C=[O:60]>[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:60])[CH3:13].[NH4+:7].[F:19][C:15]1[CH:14]=[C:13]([C@H:12]2[O:11][C:10](=[O:20])[NH:9][C@@H:8]2[C:5]2[CH:6]=[N:7][C:2]([C:22]#[C:21][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:3][CH:4]=2)[CH:18]=[CH:17][CH:16]=1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 86673453HCID 86673453, compound

Product 2

HCID 517165Ammonium AcetateHCID 69085234HCID 69085234, compoundYield 48%

Reagents, catalysts & solvents 2

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

Procedure

(4R,5R)-4-(6-chloropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (52 mg; 0.18 mmol), ethynylbenzene (20.0 mg, 0.19 mmol), bis(triphenylphosphine) palladium (II) chloride (6.2 mg, 8.88 μmol), triphenylphosphine (9.3 mg, 0.036 mmol), and copper (I) iodide (1.6 mg, 8.88 μmol) were combined in a microwave vial. dimethylformamide (0.5 mL) and diisopropylethylamine (1.5 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 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, 10.0 min=100% B, 15.0 min=100% B, Flow rate=40 mL/min) providing 31 mg (48%) (4R,5R)-5-(3-fluorophenyl)-4-(6-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one. 1H NMR (500 MHz, CDCl3) δ ppm 8.49 (1H, d, J=2.14 Hz), 7.75 (1H, dd, J=8.24, 2.44 Hz), 7.56-7.66 (3H, m), 7.32-7.46 (4H, m), 7.11 (1H, td, J=8.39, 2.44 Hz), 6.98-7.09 (2H, m), 5.34 (1H, s), 5.28 (1H, d, J=7.63 Hz), 4.79 (1H, d, J=7.32 Hz). Mass Spectral Anal. Calcd. for [M+H]+ C22H15FN2O2: 359.1. found 359.3.

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 C18 OBD 30×100 mm 5 μm

Sources & evidence

ORD record
ord-1ea56a06b6a146f48d413d31e83e4e50
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

Loading…