Tri-o-tolylphosphine → acetic acid (R)-1-{7-[(E)-(R)-4-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-3-methoxymethyl-3-methyl-4-oxo-but-1-enyl]-quinolin-2-yl}-ethyl ester

HRID 2285404Notes

Reaction equation

HRID 2285404 reaction equation
[CH:1]([C@@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10](=[O:18])[C@:11]([CH2:15][O:16][CH3:17])([CH3:14])[CH:12]=[CH2:13])([CH3:3])[CH3:2].Br[C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][C:26]([C@H:30]([O:32][C:33](=[O:35])[CH3:34])[CH3:31])=[N:27]2)=[CH:22][CH:21]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(CNCC2CCCCC2)CCCCC1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([C@@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10](=[O:18])[C@:11]([CH2:15][O:16][CH3:17])([CH3:14])/[CH:12]=[CH:13]/[C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][C:26]([C@H:30]([O:32][C:33](=[O:35])[CH3:34])[CH3:31])=[N:27]2)=[CH:22][CH:21]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphine3×HCID 4594378Bis(cyclohexylmethyl)amineHCID 86709645acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl esterHCID 86709698(R)-4-Isopropyl-3-((R)-2-methoxymethyl-2-methyl-but-3-enoyl)-oxazolidin-2-one

Product 1

HCID 86709700acetic acid (R)-1-{7-[(E)-(R)-4-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-3-methoxymethyl-3-methyl-4-oxo-but-1-enyl]-quinolin-2-yl}-ethyl esterYield 73%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst3×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of (R)-4-isopropyl-3-((R)-2-methoxymethyl-2-methyl-but-3-enoyl)-oxazolidin-2-one (226 mg, 0.769 mmol), acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl ester (196 mg, 0.666 mmol), palladium(II) acetate (35 mg, 0.154 mmol) and tri(o-tolyl)phosphine (47 mg, 0.154 mmol) were suspended in anhydrous 1,4-dioxane (15 mL) and N,N-dicyclohexylmethylamine (222 mg, 244 μL, 1.14 mmol) was added. The mixture was stirred at reflux for 90 minutes under nitrogen and more palladium(II) acetate (35 mg, 0.154 mmol) and tri(o-tolyl)phosphine (47 mg, 0.154 mmol) were added and the mixture heated for 2 h. More palladium(II) acetate (18 mg, 0.077 mmol) and tri(o-tolyl)phosphine (24 mg, 0.077 mmol) were added and heated continued for 45 minutes. The reaction was allowed to cool and diluted with ethyl acetate and washed with saturated ammonium chloride solution (2×), saturated brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 4:1 to 7:3 to give the title compound (227 mg, 73%) as a yellow foam. 1H NMR (300 MHz, CDCl3) δ 0.90 (d, J=7.1 Hz, 3H), 0.94 (d, J=7.1 Hz, 3H), 1.64 (s, 3H), 1.68 (d, J=6.7 Hz, 3H), 2.18 (s, 3H), 2.36-2.48 (m, 1H), 3.40 (s, 3H), 3.59 (d, J=8.9 Hz, 1H), 4.19 (dd, J=9.1, 3.1 Hz, 2H), 4.23-4.32 (m, 2H), 4.55-4.61 (m, 1H), 6.05 (q, J=6.7 Hz, 1H), 6.49 (d, J=16.3 Hz, 1H), 6.79 (d, J=16.3 Hz, 1H), 7.42 (d, J=8.5 Hz, 1H), 7.65 (dd, J=8.5, 1.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.94 (s, 1H), 8.11 (d, J=8.5 Hz, 1H). LCMS (m/z) 469.2 [M+H], Tr=2.91 min.

Workup

  1. temperatureat reflux for 90 minutes under nitrogen
  2. temperaturethe mixture heated for 2 h
  3. temperatureheated
  4. temperatureto cool
  5. washwashed with saturated ammonium chloride solution (2×), saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-961ac4896f97405ea6b2f40fb50f0b30
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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