Dimethyl Sulfoxide → HCID 86602487, compound

HRID 1362705Notes

Reaction equation

HRID 1362705 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([N:21]2[CH2:26][CH2:25][CH2:24]/[C:23](=[CH:27]\[C:28]3[CH:33]=[CH:32][C:31]([N:34]4[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]4)=[C:30]([O:40][CH3:41])[CH:29]=3)/[C:22]2=[O:42])[CH2:19][OH:20])=[CH:14][CH:13]=1.O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(OCC)(=O)C.C(N(CC)CC)C>[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([N:21]2[CH2:26][CH2:25][CH2:24]/[C:23](=[CH:27]\[C:28]3[CH:33]=[CH:32][C:31]([N:34]4[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]4)=[C:30]([O:40][CH3:41])[CH:29]=3)/[C:22]2=[O:42])[CH:19]=[O:20])=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 66961185HCID 66961185, compoundHCID 86585896Sodium bicarbonate water

Product 1

HCID 86602487HCID 86602487, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of dimethyl sulfoxide (0.19 mL) in methylene chloride (1 mL) was added dropwise to a solution of oxalyl chloride (167 mg) in methylene chloride (2 mL) at −78° C. The reaction solution was stirred at −78° C. for 5 minutes, and then a solution of (E)-1-(1-(4-fluorophenyl)-2-hydroxyethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one synthesized by the method described in Example 629 (260 mg) in methylene chloride (3 mL) was added dropwise to the reaction solution. The reaction solution was stirred at −78° C. for 1 hour, and then triethylamine (0.42 mL) was added to the reaction solution. The reaction solution was stirred at −78° C. for 15 minutes, and further stirred at room temperature for 45 minutes. Saturated sodium bicarbonate water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and concentrated under reduced pressure to obtain 250 mg of crude (E)-(4-fluorophenyl)-(3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-2-oxopiperidin-1-yl)acetaldehyde. p-Toluenesulfonic acid (107 mg) and ethylene glycol (0.29 mL) were added to a solution of the resulting crude (E)-(4-fluorophenyl)-(3-(3-methoxy-4-(4-methyl-1H)benzylidene)-2-oxopiperidin-1-yl)acetaldehyde (225 mg) in toluene (5 mL), and the reaction solution was heated to reflux for 1 hour and 20 minutes. After allowing the reaction solution to be cooled to room temperature, saturated sodium bicarbonate water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 7 mg of the title compound. The physical properties of the compound are as follows.

Workup

  1. additionwas added dropwise to the reaction solution
  2. stirringThe reaction solution was stirred at −78° C. for 1 hour
  3. stirringThe reaction solution was stirred at −78° C. for 15 minutes
  4. stirringfurther stirred at room temperature for 45 minutes
  5. customthe organic layer was partitioned
  6. dry with materialThe resulting organic layer was dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-65649683005c413d947a6eaed4f305c5
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

Loading…