Sodium Hydroxide → HCID 86718794, compound

HRID 1423855Notes

Reaction equation

HRID 1423855 reaction equation
[I-].C[S+](C)(C)=O.[H-].[Na+].[Cl:9][C:10]1[C:18]2[N:17]=[CH:16][N:15]([CH2:19][C@H:20]3[CH2:25][CH2:24][CH2:23][C:22](=[O:26])[CH2:21]3)[C:14]=2[CH:13]=[C:12]([C:27]#[N:28])[CH:11]=1.Br[C:30]1C=C(Cl)C2N=CN(C[C@H]3CCCC(=O)C3)C=2C=1.[OH-].[Na+]>CS(C)=O.[Cl-].[Na+].O>[O:26]1[C@:22]2([CH2:23][CH2:24][CH2:25][C@H:20]([CH2:19][N:15]3[C:14]4[CH:13]=[C:12]([C:27]#[N:28])[CH:11]=[C:10]([Cl:9])[C:18]=4[N:17]=[CH:16]3)[CH2:21]2)[CH2:30]1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 71116069HCID 71116069, compoundHCID 71116135HCID 71116135, compound

Product 1

HCID 86718794HCID 86718794, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a yellow solution of trimethylsulfoxonium iodide (1.31 g, 5.97 mmol) in DMSO (31.8 mL) under nitrogen at rt was added sodium hydride (0.239 g, 5.97 mmol). The color disappeared and bubbling occurred. Stirring was continued at rt for 30 min, and then a solution containing a mixture of 4-chloro-1-{[(1S)-3-oxocyclohexyl]methyl}-1H-benzimidazole-6-carbonitrile (1.15 g, 3.98 mmol) and (3S)-3-[(6-bromo-4-chloro-1H-benzimidazol-1-yl)methyl]cyclohexanone (1.36 g, 3.98 mmol) dissolved in DMSO (7.96 mL) was slowly added. After stirring 16 h, brine solution (25 mL) was added followed by 2 N NaOH (25 mL) to pH 13. The product was extracted into EtOAc (3×75 mL). The combined organics were washed with water (2×150 mL), dried over Na2SO4, filtered, and concentrated onto florisil for purification on a 12 g silica gel column (0-2% MeOH/DCM, 20 min gradient; 30 mL/min elution; 254 nm detection) to afford the title compound (0.735 g, 55% yield). MS (m/z) 302.1 (M+H+).

Workup

  1. custombubbling
  2. additiona solution containing
  3. additionwas slowly added
  4. stirringAfter stirring 16 h
  5. extractionThe product was extracted into EtOAc (3×75 mL)
  6. washThe combined organics were washed with water (2×150 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated onto florisil for purification on a 12 g silica gel column (0-2% MeOH/DCM, 20 min gradient; 30 mL/min elution; 254 nm detection)

Sources & evidence

ORD record
ord-1283524c945e490eb83ddfed2f425616
Source dataset
uspto-grants-2015_01
Patent number
US08927585B2

Reaction notes

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