Methanol → HCID 69968197, compound

HRID 2289138Notes

Reaction equation

HRID 2289138 reaction equation
C(OC1C=C(C=CC=1[O:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[CH:20][C:21]2[C:22]([CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[N:23][O:24][C:25]=2[C:26]=1[CH2:27][CH2:28][CH3:29])C([O-])=O)C.[C:35](Cl)(=[O:39])[C:36](Cl)=O.C(N([CH2:46][CH3:47])CC)C.[CH3:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53].C[CH:55]([OH:57])C.C[OH:59]>C(Cl)Cl.CN(C=O)C.[Cl-].[Na+].O.C([O-])(=O)C1C=CC=CC=1.[Ag+].C(OCC)(=O)C.CCCCCC>[CH2:35]([O:39][C:50]1[CH:49]=[C:48]([CH2:47][C:46]([O:57][CH3:55])=[O:59])[CH:53]=[CH:52][C:51]=1[O:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[CH:20][C:21]2[C:22]([CH2:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[N:23][O:24][C:25]=2[C:26]=1[CH2:27][CH2:28][CH3:29])[CH3:36]

Participants

11

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 21585144Isopropanol hexaneHCID 131721905HCID 131721905, compound

Product 1

HCID 69968197HCID 69968197, compound

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 164649Silver benzoateCatalystHCID 6344DichloromethaneSolventHCID 21226206Ethyl acetate hexaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 3-ethoxy-4-(3-(3-(2,2-dimethylpropyl)-7-propyl-6-benz-[4,5]-isoxazoloxy)propyloxy)benzoate (184 mg, 0.392 mmole) in methylene chloride (2 mL) and DMF (2 drops) at 0° C. was added oxalyl chloride (36 μL, 0.411 mmole). The mixture was stirred at room temperature for 30 minutes and then concentrated in vacuo. The residue was concentrated in vacuo 3× from methylene chloride The final residue was dissolved in ether (5 mL) and treated with excess diazomethane in ether until the yellow color persisted. The yellow solution was stirred at room temperature for 3 hours. Nitrogen was bubbled through the solution for 5 minutes before concentrating in vacuo. The residue was dissolved in ethyl acetate and washed with 1N sodium bicarbonate, water, brine, dried over magnesium sulfate and concentrated in vacuo to give a yellow oil. The oil was dissolved in methanol (4 mL) and triethylamine (850 μL) and stirred with silver benzoate (37 mg, 0.16 mmole) at room temperature for 18 hours. Celite and brine were added and the mixture was filtered, washing with methanol. The filtrate was concentrated in vacuo and the residue partitioned with ethyl acetate and 1N HCl. The organic phase was washed with water, brine, dried over magnesium sulfate and concentrated in vacuo to give an oil. Thin layer chromatography on silica gel eluting with hexane:2-propanol (9:1) provided the crude title compound (104 mg). A second thin layer chromatography on silica gel eluting with ethyl acetate:hexane (15:85) afforded the title compound (30 mg) as an oil. NMR (CDCl3); δ 0.96 (t, 3H); 1.07 (s, 9H); 1.41 (t, 3H); 1.69 (m, 2H); 2.35 (m, 2H); 2.82 (s, 2H); 2.87 (t, 2H); 3.56 (s, 2H); 3.70 (s, 3H); 4.06 (q, 2H); 4.25 (t, 2H); 4.29 (t, 2H); 6.80 (d, 1H); 6.83 (d, 1H); 6.88 (d, 1H); 6.95 (d, 1H); 7.37 (d, 1H).

Workup

  1. concentrationconcentrated in vacuo
  2. concentrationThe residue was concentrated in vacuo 3× from methylene chloride The final residue
  3. dissolutionwas dissolved in ether (5 mL)
  4. additiontreated with excess diazomethane in ether until the yellow color
  5. stirringThe yellow solution was stirred at room temperature for 3 hours
  6. customNitrogen was bubbled through the solution for 5 minutes
  7. concentrationbefore concentrating in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. washwashed with 1N sodium bicarbonate, water, brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customto give a yellow oil
  13. filtrationthe mixture was filtered
  14. washwashing with methanol
  15. concentrationThe filtrate was concentrated in vacuo
  16. customthe residue partitioned with ethyl acetate and 1N HCl
  17. washThe organic phase was washed with water, brine
  18. dry with materialdried over magnesium sulfate
  19. concentrationconcentrated in vacuo
  20. customto give an oil

Sources & evidence

ORD record
ord-8738585985dd4cbead775653383c41aa
Source dataset
uspto-grants-2000_07
Patent number
US06090836

Reaction notes

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