Oxalyl chloride → HCID 68544735, compound

HRID 1444760Notes

Reaction equation

HRID 1444760 reaction equation
[O:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=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:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[C:4]1[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]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 445639Oleic AcidHCID 187615452-(1,3-Oxazol-4-yl)pyridineHCID 178418339Butyllithium

Product 1

HCID 68544735HCID 68544735, compoundYield 42%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

(163) A solution of 2-(oxazol-4-yl)pyridine (4 mg, 0.027 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;030 mmol, 12 mL), and stirred for 20 min. ZnCl2 (0.5 M in THF, 2.0 equiv, 0.054 mmol, 22 mL) was added at −75° C., and stirred for 45 min at 0° C. Cul (1.0 equiv, 0.027 mmol, 5 mg) was added, and the solution was stirred for 10 min at 0° C. A separate flask was charged with oleic acid (2 equiv, 0.054 mmol, 15 mg) in anhydrous CH2Cl2 (0.5 mL), and to this solution cooled to 0° C. under N2 was added oxalyl chloride (5 equiv, 0.27 mmol, 34 mg, 24 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-2-yl)oxazol-2-yl)octadec-9-en-1-one (163) (5 mg, 0.011 mmol, 42% yield) as a brown residue: 1H NMR (CDCl3, 250 MHz) d 8.66 (br d, J=4.8 Hz,1H), 7.90-7.68 (m, 4H), 5.40-5.25 (m, 2H), 3.10 (t, J=7.4 Hz, 2H), 2.10-1.93 (m, 4H), 1.80-1.72 (m, 2H), 1.47-1.17 (m, 20H), 0.86 (br t, J=6.6 Hz, 3H); IR (CDCl3) umax 2925, 2860, 1705, 1605, 1570, 1501, 1425, 1385 cm−1; MALDI-FTMS (DHB) m/z 411.3003 (C26H38N2O2+H+ requires 411.3006).

Workup

  1. stirringstirred for 45 min at 0° C
  2. additionCul (1.0 equiv, 0.027 mmol, 5 mg) was added
  3. stirringthe solution was stirred for 10 min at 0° C
  4. stirringAfter stirring at rt for 2 h
  5. concentrationthe solution was concentrated under reduced pressure
  6. dissolutiondissolved in anhydrous THF (0.5 mL)
  7. additionThe solution of oleoyl chloride was added
  8. stirringthe solution was stirred for 1 h at 0° C
  9. additionThe reaction was diluted with EtOAc (10 mL)
  10. washwashed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL)
  11. dry with materialThe organic layer was dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4d505106b56545f1ba52609867b42f64
Source dataset
uspto-grants-2010_02
Patent number
US07662971B2

Reaction notes

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