Oxalyl chloride → HCID 68547196, compound

HRID 1444761Notes

Reaction equation

HRID 1444761 reaction equation
[O:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1.[Li]CCCC.[C:17](O)(=[O:35])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]/[CH:25]=[CH:26]\[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].C(Cl)(=O)C(Cl)=O>C1COCC1.C(Cl)Cl.[Cl-].[Cl-].[Zn+2].CO.C(Cl)Cl>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([C:4]2[N:3]=[C:2]([C:17](=[O:35])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[CH:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[O:1][CH:5]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 445639Oleic AcidHCID 450794823-(1,3-Oxazol-4-yl)pyridineHCID 178418339Butyllithium

Product 1

HCID 68547196HCID 68547196, compoundYield 23%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

(164) A solution of 3-(oxazol-4-yl)pyridine (6 mg, 0.041 mmol) in anhydrous THF (1 mL) cooled to −75° C. under N2 was treated with n-BuLi (2.5 M in hexanes, 1.1 equiv, 0.045 mmol, 18 mL), and stirred for 20 min. ZnCl2 (0.5 M in THF, 2.0 equiv, 0.082 mmol, 33 mL) was added at −75° C., and stirred for 45 min at 0C. Cul (1.0 equiv, 0.041 mmol, 8 mg) was added, and the solution was stirred for 10 min at 0° C. A separate flask was charged with oleic acid (2 equiv, 0.082 mmol, 23 mg) in anhydrous CH2Cl2 (0.5 mL), and to this solution cooled to 0° C. under N2 was added oxalyl chloride (5 equiv, 0.41 mmol, 52 mg, 37 mL). After stirring at rt for 2 h, the solution was concentrated under reduced pressure and dissolved in anhydrous THF (0.5 mL). The solution of oleoyl chloride was added and the solution was stirred for 1 h at 0° C. The reaction was diluted with EtOAc (10 mL), and washed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. Flash chromatography (SiO2, 1.5 cm×17.5 cm, 2% MeOH—CH2Cl2) afforded 1-(4-(pyridin-3-yl)oxazol-2-yl)octadec-9-en-1-one (164) (4 mg, 0.009 mmol, 23% yield) as a brown residue: 1H NMR (CDCl3, 250 MHz) d 8.99 (br s, 1H), 8.65 (br d, J=4.7 Hz, 1H), 8.04 (br d, J=7.5 Hz, 1H), 7.86-7.54 (m, 2H), 5.41-5.26 (m, 2H), 3.10 (t, J=7.4 Hz, 2H), 2.10-1.93 (m, 4H), 1.83-1.70 (m, 2H), 1.45-1.20 (m, 20H), 0.86 (br t, J=6.6 Hz, 3H); IR (CDCl3) umax 2926, 2871, 1700, 1601, 1564, 1510, 1421, 1382 cm−1; MALDI-FTMS (DHB) m/z 411.3012 (C26H38N2O2+H+ requires 411.3006).

Workup

  1. additionCul (1.0 equiv, 0.041 mmol, 8 mg) was added
  2. stirringthe solution was stirred for 10 min at 0° C
  3. stirringAfter stirring at rt for 2 h
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutiondissolved in anhydrous THF (0.5 mL)
  6. additionThe solution of oleoyl chloride was added
  7. stirringthe solution was stirred for 1 h at 0° C
  8. additionThe reaction was diluted with EtOAc (10 mL)
  9. washwashed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL)
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-65b7ddca2970418982bc19a03dda5009
Source dataset
uspto-grants-2010_02
Patent number
US07662971B2

Reaction notes

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