Dimethyl Sulfoxide → HCID 66582622, compound

HRID 1972511Notes

Reaction equation

HRID 1972511 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[S:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[S:16]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([OH:37])([CH3:36])[C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=2)[C@@H:21]([CH2:38][N:39]2[CH2:44][CH2:43][CH:42]([OH:45])[CH2:41][CH2:40]2)[CH2:20]1)(=[O:18])=[O:17].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[S:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[S:16]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([OH:37])([CH3:36])[C:32]([F:33])([F:34])[F:35])=[CH:27][CH:26]=2)[C@@H:21]([CH2:38][N:39]2[CH2:40][CH2:41][C:42](=[O:45])[CH2:43][CH2:44]2)[CH2:20]1)(=[O:17])=[O:18]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 665825261-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-4-piperidinol

Product 1

HCID 66582622HCID 66582622, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 2.0 M solution of oxalyl chloride in CH2Cl2 (162 μL, 0.323 mmol, Sigma-Aldrich, St. Louis, Mo.) was diluted with CH2Cl2 and then chilled to −78° C. To this solution was added DMSO (45.9 μL, 0.647 mmol). The mixture was stirred for 30 min, and then a solution of 1-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-4-piperidinol (115 mg, 0.216 mmol) in CH2Cl2 was added to slowly to the mixture. The reaction was stirred for 1 h at −78° C. and then triethylamine (150 μl, 1.078 mmol) was added. Afterwards, the mixture was stirred for 15 min and allowed to slowly warm to room temperature and stirred for additional 4 h. Saturated aqueous NaHCO3 was added and the mixture was concentrated. The crude material was absorbed onto silica gel and purified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 1-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-4-piperidinone (40 mg) as a mixture of two isomers.

Workup

  1. stirringThe reaction was stirred for 1 h at −78° C.
  2. stirringAfterwards, the mixture was stirred for 15 min
  3. temperatureto slowly warm to room temperature
  4. stirringstirred for additional 4 h
  5. concentrationthe mixture was concentrated
  6. customThe crude material was absorbed onto silica gel
  7. custompurified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-4e752040a0f04587b7d48b46d0edf7f2
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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