Diethylamine → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one

HRID 604654Notes

Reaction equation

HRID 604654 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]#[CH:21])[C@H:14]2[CH3:22])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[C:29]([F:35])=[CH:28][C:27]=1[O:36][CH3:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NCC)C>CN(C=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>[F:24][C:2]([F:1])([F:23])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]#[C:21][C:26]3[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[C:29]([F:35])=[CH:28][C:27]=3[O:36][CH3:37])[C@H:14]2[CH3:22])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

8

Reactant 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 573894991-Bromo-4-fluoro-5-isopropyl-2-methoxybenzeneHCID 86627632(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-prop-2-yn-1-yl-1,3-oxazolidin-2-one

Product 1

HCID 86627633(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-prop-2-yn-1-yl-1,3-oxazolidin-2-one (100 mg, 0.285 mmol), 1-bromo-4-fluoro-5-isopropyl-2-methoxybenzene (27.4 wt % in toluene, 233 mg, 0.259 mmol), bis(triphenylphosphine)palladium dichloride (18.2 mg, 0.0259 mmol), copper (I) iodide (4.9 mg, 0.0259 mmol), triphenylphosphine (13.6 mg, 0.0518 mmol), and diethylamine (283 mg, 406 μL, 3.88 mmol) in dry DMF (0.5 mL) was degassed and subjected to microwave irradiation (120° C., 60 min). The reaction mixture was diluted with 0.1N HCl (10 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.38 (20% EtOAc/hexanes). LCMS calc.=518.2; found=518.2 (M+1)+. 1H NMR (500 MHz, CDCl3): δ 7.89 (s, 1H); 7.78 (s, 2H); 7.26 (d, J=8.4 Hz, 1H); 6.56 (d, J=12.0 Hz, 1H); 5.76 (d, J=8.3 Hz, 1H); 4.70 (d, J=17.8 Hz, 1H); 4.53-4.47 (m, 1H); 4.08 (d, J=17.8 Hz, 1H); 3.82 (s, 3H); 3.17-3.09 (m, 1H); 1.22 (d, J=6.9 Hz, 6H); 0.90 (d, J=6.5 Hz, 3H).

Workup

  1. customwas degassed
  2. customsubjected to microwave irradiation (120° C., 60 min)
  3. additionThe reaction mixture was diluted with 0.1N HCl (10 mL)
  4. extractionextracted with EtOAc (3×20 mL)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customThis was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-8786452692c9438cb59bb6dd051f5a7d
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

Loading…