Lithium Hexamethyldisilazide → 3-fluoro-N-(4-methoxybenzyl)-4-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 528518Notes

Reaction equation

HRID 528518 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[S:13][N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:26][C:27]1[CH:28]=[C:29]([S:36](Cl)(=[O:38])=[O:37])[CH:30]=[CH:31][C:32]=1[N+:33]([O-:35])=[O:34]>C1COCC1>[F:26][C:27]1[CH:28]=[C:29]([S:36]([N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=2)[C:9]2[S:13][N:12]=[CH:11][N:10]=2)(=[O:37])=[O:38])[CH:30]=[CH:31][C:32]=1[N+:33]([O-:35])=[O:34]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 155695553-Fluoro-4-nitrobenzenesulfonyl chlorideHCID 65271538N-(4-Methoxybenzyl)-1,2,4-thiadiazol-5-amine2×

Product 1

HCID 897620223-fluoro-N-(4-methoxybenzyl)-4-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 250-mL round bottom flask was charged with N-(4-methoxybenzyl)-1,2,4-thiadiazol-5-amine (INTERMEDIATE H, 2.032 g, 9.18 mmol) and THF (30 mL). The flask was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in THF) (10.02 mL, 10.02 mmol) was added dropwise, rapidly. The flask was placed in an ice/water bath for 10 minutes, and then returned to −78° C., at which time a solution of 3-fluoro-4-nitrobenzenesulfonyl chloride (Matrix Scientific, Columbia, S.C., 2.000 g, 8.35 mmol) in THF (5 mL with a 1 mL wash) was added dropwise. After 15 minutes, the reaction was complete, and was quenched with aqueous saturated ammonium chloride solution. The mixture was warmed to RT and extracted with EtOAc. The organics were combined and dried over sodium sulfate, filtered and concentrated. The solids were taken up in methanol, and after triturating, were filtered and washed with methanol to yield 3-fluoro-N-(4-methoxybenzyl)-4-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide. (INTERMEDIATE I) (2.76 g, 6.50 mmol) as a light yellow solid. m/z (ESI) 446.7 (M+Na)+.

Workup

  1. customreturned to −78° C., at which time
  2. washwash)
  3. additionwas added dropwise
  4. waitAfter 15 minutes
  5. customwas quenched with aqueous saturated ammonium chloride solution
  6. temperatureThe mixture was warmed to RT
  7. extractionextracted with EtOAc
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customafter triturating
  12. filtrationwere filtered
  13. washwashed with methanol

Sources & evidence

ORD record
ord-3c8ef9de95f04b258edec20e265dd38c
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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