Dimethyl Sulfoxide → HCID 68958974, compound

HRID 2378062Notes

Reaction equation

HRID 2378062 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([Si:15]([CH3:42])([CH3:41])[O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:26]([C:34]3([CH:37]([OH:40])[CH2:38][CH3:39])[CH2:36][CH2:35]3)[O:25][N:24]=2)=[CH:19][CH:18]=1)([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl.O>[C:11]([Si:15]([CH3:42])([CH3:41])[O:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:26]([C:34]3([C:37](=[O:40])[CH2:38][CH3:39])[CH2:36][CH2:35]3)[O:25][N:24]=2)=[CH:21][CH:22]=1)([CH3:12])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68959536HCID 68959536, compound

Product 1

HCID 68958974HCID 68958974, compoundYield 96.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirring solution consisting of oxalyl chloride (5.0 mL) in dichloromethane (115 mL) at −78° C. is added dropwise a solution consisting of dimethyl sulfoxide (8.2 mL) in dichloromethane (25 mL) over ten minutes. The mixture is stirred at −78° C. for 40 minutes and a solution consisting of (±)-1-(1-{3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-4-phenyl-isoxazol-5-yl}-cyclopropyl)-propan-1-ol (synthetic intermediate prepared in Example 47, 18.70 g) in dichloromethane (150 mL) is subsequently added dropwise over one hour. The mixture is stirred at −78° C. for an additional 30 minutes and excess triethylamine is subsequently added dropwise. The stirring mixture is allowed to warm gradually to room temperature overnight. The stirring mixture is treated with water. The layers are separated and the aqueous layer is extracted with a fresh portion of dichloromethane. The combined organic extracts are washed with brine solution, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate is purified by flash silica gel column chromatography. Elution with hexanes-ethyl acetate (17:3 v/v) afforded the synthetic intermediate 1-(1-{3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-4-phenyl-isoxazol-5-yl}-cyclopropyl)-propan-1-one (17.90 g.)

Workup

  1. additionis added dropwise a solution
  2. additionis subsequently added dropwise over one hour
  3. stirringThe mixture is stirred at −78° C. for an additional 30 minutes
  4. temperatureto warm gradually to room temperature overnight
  5. customThe layers are separated
  6. extractionthe aqueous layer is extracted with a fresh portion of dichloromethane
  7. washThe combined organic extracts are washed with brine solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe concentrate is purified by flash silica gel column chromatography
  12. washElution with hexanes-ethyl acetate (17:3 v/v)

Sources & evidence

ORD record
ord-45b053812c60482abbd763ea6780e417
Source dataset
uspto-grants-2008_12
Patent number
US07470715B2

Reaction notes

Loading…