Methanol → HCID 53419529, compound

HRID 2215774Notes

Reaction equation

HRID 2215774 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][CH:9]=[CH:8]2.C(Cl)(=O)[C:13](Cl)=[O:14].[CH3:18][O-:19].[Na+].[CH3:21][OH:22]>CCOCC.CCOC(C)=O>[CH3:18][O:19][C:13](=[O:14])[C:21]([C:8]1[C:7]2[C:11](=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][CH:6]=2)[NH:10][CH:9]=1)=[O:22]

Participants

7

Reactant 4

HCID 887MethanolHCID 65578Oxalyl chloride2×HCID 766607-Methoxy-1H-indoleHCID 10942334Sodium Methoxide

Product 1

HCID 53419529HCID 53419529, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 7-methoxy-indole (1.10 g, 7.47 mmol) in Et2O (150 mL) cooled to 0–5° C. was treated with oxalyl chloride (0.75 mL, 8.6 mmol). After 30 min, the mixture was allowed to warm to room temperature and stirred 1 h. Additional oxalyl chloride (0.25 mL, 2.87 mmol) was added, the mixture stirred an additional 1 h and then cooled to −78° C. A 25% solution of sodium methoxide in methanol (5.4 mL, 23.8 mmol) was added over 10 min. The suspension was warmed to room temperature, stirred 2 h and then poured into EtOAc/pH 7 buffer. The EtOAc layer was separated and washed with water, brine, dried (MgSO4), filtered and concentrated to ˜20 mL. The resulting slurry was diluted with Et2O (75 mL), and filtered. The solid obtained was washed with Et2O and dried under vacuum overnight to afford the title compound as an off-white solid (1.23 g, 71%). Upon standing, the mother liquor afforded a second crop (0.26 g, 15%). 1H NMR (400 MHz, DMSO-d6) 12.63 (br s, 1H), 8.29 (d, J=3.5 Hz, 1H), 7.73 (d, J=8 Hz, 1H), 7.20 (dd, J=8, 8 Hz, 1H), 6.89 (d, J=8 Hz, 1H). 13C NMR (75.5 MHz, DMSO-d6) 178.72, 163.88, 146.37, 137.19, 127.02, 125.54, 123.73, 113.52, 112.92, 104.60, 55.34, 52.42. IR (CHCl3, cm−1) 3452, 1732, 1648. MS (electrospray, m/z) 234.1 (M++1), 232.2 (M−−1). Anal. Calcd for C12H11NO4: C, 61.80; H, 4.75; N, 6.01. Found: C, 61.61; H, 4.83; N, 6.01.

Workup

  1. stirringthe mixture stirred an additional 1 h
  2. temperaturecooled to −78° C
  3. temperatureThe suspension was warmed to room temperature
  4. stirringstirred 2 h
  5. customThe EtOAc layer was separated
  6. washwashed with water, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to ˜20 mL
  10. additionThe resulting slurry was diluted with Et2O (75 mL)
  11. filtrationfiltered
  12. customThe solid obtained
  13. washwas washed with Et2O
  14. customdried under vacuum overnight

Sources & evidence

ORD record
ord-fb64e1e1ff02425aaaa6b0cb2aacea53
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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