Triethylamine → (+)-(4R,5R)-5-(3-Methoxyphenyl)-4-(3-(phenylethynyl)phenyl)oxazolidin-2-one

HRID 2362436Notes

Reaction equation

HRID 2362436 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]=[C:15]([O:19][CH3:20])[CH:14]=3)[O:11][C:10](=[O:21])[NH:9]2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:48]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)#[CH:49]>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>[CH3:20][O:19][C:15]1[CH:14]=[C:13]([C@H:12]2[O:11][C:10](=[O:21])[NH:9][C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:49]#[C:48][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[CH:3]=2)[CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 69082831(+)-(4R,5R)-4-(3-bromophenyl)-5-(3-methoxyphenyl)oxazolidin-2-one

Product 1

HCID 69083418(+)-(4R,5R)-5-(3-Methoxyphenyl)-4-(3-(phenylethynyl)phenyl)oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

A suspension of (+)-(4R,5R)-4-(3-bromophenyl)-5-(3-methoxyphenyl)oxazolidin-2-one (2.4 g, 6.89 mmol) in triethylamine (24 mL, 172 mmol) was purged with nitrogen for 1 h (volume dropped by ca. 5 mL). The reaction was treated with triphenylphosphine (0.152 g, 0.579 mmol) and ethynylbenzene (0.776 mL, 7.07 mmol), and purged 10 minutes longer. To this was added PdCl2(PPh3)2 (0.034 g, 0.048 mmol) and copper(I) iodide (7.88 mg, 0.041 mmol). After purging 10 min longer, the reaction was warmed to a vigorous reflux. The reaction was heated at reflux overnight. In the morning, the reaction was cooled to room temperature, diluted with diethyl ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%-->40% EtOAc/Hex) gave 2.2 g (80%) as a colorless foam solid. 1H-NMR (CDCl3, 500 MHz) δ 7.56 (m, 4H), 7.36-7.45 (m, 4H), 7.34 (m, 1H), 7.30 (m, 1H), 6.92-6.98 (m, 1H), 6.85-6.90 (m, 2H), 5.93 (bs, 1H), 5.31 (d, J=7.3, 1H), 4.78 (d, J=7.3, 1H), 3.84 (s, 3H). 13C-NMR (CDCl3, 126 MHz) δ 160.2, 158.6, 138.92, 138.85, 132.3, 131.8, 130.2, 129.6, 129.4, 128.7, 128.5, 126.4, 124.6, 122.9, 118.1, 115.0, 111.2, 90.6, 88.6, 85.9, 64.6, 55.5. Mass spec.: 370.18 (MH)+.

Workup

  1. customwas purged with nitrogen for 1 h
  2. addition(volume dropped by ca. 5 mL)
  3. custompurged 10 minutes longer
  4. customAfter purging 10 min longer
  5. temperaturethe reaction was warmed to a vigorous reflux
  6. temperatureThe reaction was heated
  7. temperatureat reflux overnight
  8. additiondiluted with diethyl ether
  9. washwashed with water (3×)
  10. dry with materialbrine, dried over magnesium sulfate
  11. concentrationconcentrated
  12. customColumn chromatography (25%-->40% EtOAc/Hex) gave 2.2 g (80%) as a colorless foam solid

Sources & evidence

ORD record
ord-51f25422bfe843af8a64260877308956
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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