Potassium hydride → HCID 58107417, compound

HRID 873680Notes

Reaction equation

HRID 873680 reaction equation
[H-].[K+].Br[C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1.C([Li])(C)(C)C.[Cl:18][C:19]1[CH:30]=[CH:29][C:22]([C:23](N(OC)C)=[O:24])=[CH:21][C:20]=1[S:31](=[O:34])(=[O:33])[NH2:32]>O1CCCC1>[Cl:18][C:19]1[CH:30]=[CH:29][C:22]([C:23]([C:4]2[CH:12]=[C:11]3[C:7]([CH:8]=[CH:9][NH:10]3)=[CH:6][CH:5]=2)=[O:24])=[CH:21][C:20]=1[S:31]([NH2:32])(=[O:34])=[O:33]

Participants

6

Reactant 4

HCID 82127Potassium hydrideHCID 6764936-BromoindoleHCID 581073994-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamideHCID 178418306HCID 178418306, compound

Product 1

HCID 58107417HCID 58107417, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A dispersion of potassium hydride in oil (33.15 mmol) is washed with hexanes under argon then tetrahydrofuran (310 mL) is added at 0° C. and the resulting suspension is treated by dropwise addition of 6.77 g of 6-bromoindole in tetrahydrofuran (61 mL). The reaction mixture is stirred at 0° C. for 15 min to give a yellow solution. A solution of 44.2 mL of tert-butyllithium (1.5 M in pentane) is added slowly at −78° C. while maintaining the temperature below −75° C. to produce a yellow suspension. After 15 min a solution of 3.08 g of 4-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamide in tetrahydrofuran (61 mL) is added and the temperature is allowed to increase slowly to 0° C. The reaction mixture is quenched by addition of 62 mL of saturated aqueous ammonium chloride and extracted with ethyl ether. The organics were washed with water, dried over magnesium sulfate and concentrated to 9.65 g of a brown oil which is chromatographed on silica gel (1:1 hexanes/ethyl acetate) to give 2-chloro-5-(1H-indole-6-carbonyl)-benzenesulfonamide as a yellow foam. MS (m/z): 333 (M−1); Rf 0.37 (1:1 hexanes/ethyl acetate).

Workup

  1. customto give a yellow solution
  2. temperaturewhile maintaining the temperature below −75° C.
  3. customto produce a yellow suspension
  4. temperatureto increase slowly to 0° C
  5. customThe reaction mixture is quenched by addition of 62 mL of saturated aqueous ammonium chloride
  6. extractionextracted with ethyl ether
  7. washThe organics were washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated to 9.65 g of a brown oil which
  10. customis chromatographed on silica gel (1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-eabca3465dd84d4baae40b023b896396
Source dataset
uspto-grants-2015_03
Patent number
US08975439B2

Reaction notes

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