Acetyl chloride → HCID 58044136, compound

HRID 1918895Notes

Reaction equation

HRID 1918895 reaction equation
[C:1]1(=[O:14])[C:6]2=[N:7][C:8]3[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=3[N:5]2[CH2:4][CH2:3][NH:2]1.[C:15]([O:18][CH2:19][C:20]1[C:25]([Br:26])=[CH:24][CH:23]=[CH:22][C:21]=1Br)(=[O:17])[CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC.C(Cl)(=O)C.C(N(CC)CC)C>C(Cl)Cl.C(=O)(O)[O-].[Na+].[Cu](I)I.O1CCOCC1>[C:15]([O:18][CH2:19][C:20]1[C:21]([N:2]2[CH2:3][CH2:4][N:5]3[C:6](=[N:7][C:8]4[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=43)[C:1]2=[O:14])=[CH:22][CH:23]=[CH:24][C:25]=1[Br:26])(=[O:17])[CH3:16]

Participants

11

Reactant 6

HCID 6367Acetyl chlorideHCID 8070N,N'-DimethylethylenediamineHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 58044127HCID 58044127, compoundHCID 592164132,6-Dibromobenzyl acetate

Product 1

HCID 58044136HCID 58044136, compoundYield 13.2%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 152c (485 mg, 2.54 mmol), 104g (1.56 g, 5.08 mmol), cesium carbonate (1.66 g, 5.08 mmol), N,N′-dimethylethylene-diamine (447 mg, 5.08 mmol) and 1,4-dioxane (20 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper iodide (484 mg, 2.54 mmol) was added, and the reaction mixture was heated at 100° C. (oil bath temperature) for 16 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (100 mL) and water (50 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a yellow oil, which was dissolved in methylene chloride (5 mL). Acetyl chloride (506 mg, 2.54 mmol) and triethylamine (1.28 g, 12.7 mmol) were added, and the reaction mixture was stirred at room temperature for 2 h. After this time, the reaction mixture was diluted with methylene chloride (50 mL) and saturated aqueous sodium bicarbonate (20 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford a 13% yield (140 mg) of 152d as a yellow oil: 1H NMR (500 MHz, CDCl3) d 7.60 (d, 1H, J=8.0 Hz), 7.27 (t, 1H, J=8.0 Hz), 7.18 (d, 1H, J=8.0 Hz), 5.26 (d, 1H, J=12.0 Hz), 5.14 (d, 1H, J=12.0 Hz), 4.32 (m, 1H), 4.24 (m, 1H), 4.14 (m, 1H), 3.87 (m, 1H), 2.75 (m, 2H), 2.56 (m, 2H), 2.07 (s, 3H), 1.83 (m, 4H); MS (APCI+) m/z 418.8 (M+H).

Workup

  1. customA 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet
  2. customAfter bubbling nitrogen through the resulting suspension for 30 min
  3. temperatureAfter this time, the mixture was cooled to room temperature
  4. filtrationfiltered
  5. additionThe filtrate was diluted with ethyl acetate (100 mL) and water (50 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography
  11. customto afford a yellow oil, which
  12. customThe organic layer was separated
  13. extractionthe aqueous layer was extracted with methylene chloride (3×50 mL)
  14. dry with materialThe combined organic layers were dried over sodium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-93dd9ec6d22d43e188018f5fadf4eb84
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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