4-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamide → 2-Chloro-5-[4-(3-methyl-piperidin-1-yl)-benzoyl]-benzenesulfonamide

HRID 873657Notes

Reaction equation

HRID 873657 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([CH3:14])[CH2:9]2)=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:27]=[CH:26][C:19]([C:20](N(OC)C)=[O:21])=[CH:18][C:17]=1[S:28](=[O:31])(=[O:30])[NH2:29].C([Li])(C)(C)C>O1CCCC1>[Cl:15][C:16]1[CH:27]=[CH:26][C:19]([C:20](=[O:21])[C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][CH2:11][CH:10]([CH3:14])[CH2:9]3)=[CH:4][CH:3]=2)=[CH:18][C:17]=1[S:28]([NH2:29])(=[O:31])=[O:30]

Participants

5

Reactant 3

HCID 581073994-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamideHCID 668503451-(4-Bromo-phenyl)-3-methyl-piperidineHCID 178418306HCID 178418306, compound

Product 1

HCID 581074352-Chloro-5-[4-(3-methyl-piperidin-1-yl)-benzoyl]-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.821 g of 1-(4-bromo-phenyl)-3-methyl-piperidine in tetrahydrofuran is cooled to −78° C. and treated with 0.3 g of 4-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamide. The mixture is stirred for 10 min and treated slowly with 4.31 mL of a solution of tert-butyl lithium (1.5 M) in tetrahydrofuran (3 mL). The orange solution is stirred at −78° C. for 15 min then at 0° C. for 1 hour. The reaction mixture is quenched with saturated aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (2×50 mL). The organics are washed with water, a saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is loaded on Celite and purified by silica gel chromatography (1:1 hexanes/ethyl acetate) to give 2-chloro-5-[4-(3-methyl-piperidin-1-yl)-benzoyl]-benzenesulfonamide as a light yellow syrup. MS (m/z): 393 (M+1). HPLC Reverse Phase (Nucleosil 100-5 C18, gradient 10→100% CH3CN in 5 min) room temperature=5.40 minutes.

Workup

  1. stirringThe orange solution is stirred at −78° C. for 15 min
  2. waitat 0° C. for 1 hour
  3. customThe reaction mixture is quenched with saturated aqueous ammonium chloride (100 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe organics are washed with water
  6. dry with materiala saturated sodium chloride solution, dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by silica gel chromatography (1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-3f47d0f01eb34dffb08f47ac75054455
Source dataset
uspto-grants-2015_03
Patent number
US08975439B2

Reaction notes

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