Methanol → HCID 69642180, compound

HRID 2215766Notes

Reaction equation

HRID 2215766 reaction equation
[C:1](Cl)(=[O:5])C(Cl)=O.[Br:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:16]=1[NH:15][CH:14]=[CH:13]2.[CH3:17][O-:18].[Na+].[CH3:20][OH:21]>CCOCC.CCOC(C)=O.O>[CH3:17][O:18][C:1](=[O:5])[C:20]([C:13]1[C:12]2[C:16](=[C:8]([Br:7])[CH:9]=[CH:10][CH:11]=2)[NH:15][CH:14]=1)=[O:21]

Participants

8

Reactant 4

HCID 887MethanolHCID 65578Oxalyl chlorideHCID 27570207-BromoindoleHCID 10942334Sodium Methoxide

Product 1

HCID 69642180HCID 69642180, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

Oxalyl chloride (1.8 mL, 20.7 mmol) was added dropwise to a solution of 7-bromoindole (3.65 g, 18.6 mmol) in Et2O (100 mL) cooled in an ice bath. After the addition was complete, the ice bath was removed and the mixture was allowed to warm to room temperature and stirred for 8 h. The mixture was then cooled in a dry ice-acetone bath and a 25% by wt solution of sodium methoxide in methanol (9.5 mL, 41.8 mmol) added dropwise over 5 min. The suspension was allowed to warm to room temperature affording a yellow suspension. After stirring 1 h at rt, the suspension was treated with water and the mixture poured into EtOAc. The EtOAc solution was separated and washed with pH 7.0 buffer and brine, dried (MgSO4) and concentrated to ˜75 mL. The solution was diluted with Et2O and allowed to stand. Filtration afforded the title compound as pale yellow crystals (0.61 g, 12%). Concentration of the mother liquor to a slurry followed by addition of a small amount of Et2O (20 mL) and filtration afforded a second crop (2.33 g, 44%). 1H NMR (400 MHz, DMSO-d6) 12.68 (br s, 1H), 8.46 (br s, 1H), 8.17 (d, J=8 Hz, 1H), 7.54 (d, J=8 Hz, 1H), 7.23 (dd, J=8, 8 Hz, 1H), 3.90 (s, 3H). 13C NMR (75.5 MHz, DMSO-d6) 178.63, 163.34, 138.72, 135.06, 127.16, 126.45, 124.27, 120.51, 113.22, 105.03, 52.59. IR (CHCl3, cm−1) 3450, 1731, 1654. MS (electrospray, m/z) 284/282 (M++1), 282/280 (M−−1). HRMS 281.9786 (M++1, calcd for C11H9NO3Br 281.9766). Anal. Calcd for C11H8BrNO3: C, 46.84; H, 2.86; N, 4.97. Found: C, 46.81; H, 2.72; N, 4.91.

Workup

  1. temperaturecooled in an ice bath
  2. additionAfter the addition
  3. customthe ice bath was removed
  4. temperatureThe mixture was then cooled in a dry ice-acetone bath
  5. temperatureto warm to room temperature
  6. customaffording a yellow suspension
  7. stirringAfter stirring 1 h at rt
  8. customThe EtOAc solution was separated
  9. washwashed with pH 7.0 buffer
  10. dry with materialbrine, dried (MgSO4)
  11. concentrationconcentrated to ˜75 mL
  12. additionThe solution was diluted with Et2O
  13. filtrationFiltration

Sources & evidence

ORD record
ord-c268cf885f6c46ad9dc067f7c9cf1ef7
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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