Dimethyl Sulfoxide → HCID 21069245, compound

HRID 1244173Notes

Reaction equation

HRID 1244173 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([C:18]1([S:24]([N:27]2[CH2:32][CH2:31][CH:30]([CH2:33][CH2:34][CH2:35][OH:36])[CH2:29][CH2:28]2)(=[O:26])=[O:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:11]([O:15][C:16]([C:18]1([S:24]([N:27]2[CH2:28][CH2:29][CH:30]([CH2:33][CH2:34][CH:35]=[O:36])[CH2:31][CH2:32]2)(=[O:26])=[O:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 21069244HCID 21069244, compound

Product 1

HCID 21069245HCID 21069245, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
65 °C

Procedure

A 50 mL round-bottom flask was charged with oxalyl chloride (0.4 mL, 3.82 mmol) and methylene chloride (9 mL). The flask was then immersed into a dry ice/acetone bath. Afterward, dimethylsulfoxide (0.54 mL, 7.7 mmol) was added dropwise, maintaining the temperature at less than −65° C. After complete addition, the mixture was stirred for 15 min. A solution of the alcohol from Example A7 (1.50 g, 3.82 mmol) in methylene chloride (9 mL) was then added dropwise while maintaining the temperature at less than-65° C. The resulting mixture was stirred for 45 min after complete addition. Diisopropylethylamine (3.3 mL, 19 mmol) was then added dropwise. Subsequently, the mixture was stirred for 30 min with cooling. The dry ice/acetone bath was then removed. After 1 hr, the reaction mixture was diluted with methylene chloride (50 mL) and extracted with water (50 mL). The aqueous layer was re-extracted with methylene chloride (25 mL). The combined organic layers were then dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography using a gradient of 10–30% ethyl acetate/hexane afforded a white crystalline solid (1.24 g, 83% yield). 1H NMR (CDCl3) δ 1.20–1.42 (m, 5H), 1.51 (s, 9H), 1.53–1.59 (m, 2H), 1.68 (d, J=11.2 Hz, 2H), 2.10 (td, J=4.5, 12.8 Hz, 2H), 2.31 (d, J=11.2 Hz, 2H), 2.92 (t, J=12.6 Hz, 2H), 3.30 (t, J=12.4 Hz, 2H), 3.62 (t, J=6.6 Hz, 2H), 3.76 (d, J=12 Hz), 3.95 (dd, J=4, 11.6 Hz, 2H); Electrospray mass spectrometry showed m/z=390 (M+H).

Workup

  1. customThe flask was then immersed into a dry ice/acetone bath
  2. temperaturemaintaining the temperature at less than −65° C
  3. additionAfter complete addition
  4. stirringThe resulting mixture was stirred for 45 min
  5. additionafter complete addition
  6. stirringSubsequently, the mixture was stirred for 30 min
  7. temperaturewith cooling
  8. customThe dry ice/acetone bath was then removed
  9. waitAfter 1 hr
  10. additionthe reaction mixture was diluted with methylene chloride (50 mL)
  11. extractionextracted with water (50 mL)
  12. extractionThe aqueous layer was re-extracted with methylene chloride (25 mL)
  13. dry with materialThe combined organic layers were then dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-cee0b4073ede49a580f2b36e8e5a39fe
Source dataset
uspto-grants-2006_10
Patent number
US07119203B2

Reaction notes

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