4-Methoxybenzenesulfonyl chloride → HCID 51355175, compound

HRID 2077600Notes

Reaction equation

HRID 2077600 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][S:28]([C:25]2[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=2)(=[O:30])=[O:29])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 218583543-Amino-5-bromo-2-chloropyridine

Product 1

HCID 51355175HCID 51355175, compoundYield 68.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A round bottom flask was charged with 5-bromo-2-chloropyridin-3-amine (2.50 g, 12.1 mmol) and 24 mL THF and the solution was cooled to −78° C. under nitrogen. 1.0 M LiHMDS (24.1 ml, 24.1 mmol) was added slowly and the solution was stirred for 10 min at −78° C. 4-methoxybenzene-1-sulfonyl chloride (3.49 g, 16.9 mmol) dissolved in a minimum amount of THF (˜5 mL) was added slowly, and the cooling bath was removed after 10 min. The reaction was stirred at room temperature overnight and was quenched with saturated NH4Cl. The layers were separated, and the organic portion was diluted with CH2Cl2, washed with 1 N HCl and brine. The organic portion was dried with MgSO4, filtered and concentrated. The crude material was dissolved in CH2Cl2 (˜20 mL) and ether was added (˜40 mL) in portions over 15 min. After allowing to stand in the freezer for 1 h, the solids were filtered and washed with ether. N-(5-bromo-2-chloropyridin-3-yl)-4-methoxybenzenesulfonamide (3.127 g, 68.7% yield) was isolated as a white crystalline solid. MS (ESI pos. ion) m/z calc'd for C12H10BrClN2O3S: 377.6. found 378.8.

Workup

  1. additionwas added slowly
  2. customthe cooling bath was removed after 10 min
  3. stirringThe reaction was stirred at room temperature overnight
  4. customwas quenched with saturated NH4Cl
  5. customThe layers were separated
  6. additionthe organic portion was diluted with CH2Cl2
  7. washwashed with 1 N HCl and brine
  8. dry with materialThe organic portion was dried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe crude material was dissolved in CH2Cl2 (˜20 mL)
  12. additionether was added (˜40 mL) in portions over 15 min
  13. waitto stand in the freezer for 1 h
  14. filtrationthe solids were filtered
  15. washwashed with ether

Sources & evidence

ORD record
ord-d5bb14a9a03b4aab935ceaae01a1d034
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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