Hydrochloric Acid → 5-amino-3-(2-fluoro-5-nitrophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide

HRID 627595Notes

Reaction equation

HRID 627595 reaction equation
[C:1]([C:3]([S:6]([CH2:9][C:10]([NH:22]S(C(C)(C)C)=O)([C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=1[F:21])[CH3:11])(=[O:8])=[O:7])([CH3:5])[CH3:4])#[N:2].Cl>CO.[Cu]Cl>[NH2:2][C:1]1[C:3]([CH3:5])([CH3:4])[S:6](=[O:8])(=[O:7])[CH2:9][C:10]([C:12]2[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=2[F:21])([CH3:11])[N:22]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86728094N-(1-((2-cyanopropan-2-yl)sulfonyl)-2-(2-fluoro-5-nitrophenyl)propan-2-yl)-2-methylpropane-2-sulfinamide

Product 1

HCID 771429635-amino-3-(2-fluoro-5-nitrophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxideYield 99%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 887MethanolSolvent

Procedure

A suspension of N-(1-((2-cyanopropan-2-yl)sulfonyl)-2-(2-fluoro-5-nitrophenyl)propan-2-yl)-2-methylpropane-2-sulfinamide (560 mg, 1.292 mmol) in MeOH (10 ml) was treated with hydrogen chloride (4M in 1,4-dioxane) (3.23 ml, 12.92 mmol) for 1 h at RT. The mixture was concentrated in the stream of nitrogen, redissolved in 10 ml EtOH and copper (I) chloride (134 mg, 1.356 mmol) was added. The mixture was sonicated for 5 min, and heated at reflux for 2 h. After concentrating in vacuo, the residue was partitioned between 10 ml DCM and 10 ml 2N NaOH solution. The organic layer was separated, washed with brine and concentrated to afford crude 5-amino-3-(2-fluoro-5-nitrophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (420 mg, 1.275 mmol, 99% yield), which was used without further purification.

Workup

  1. concentrationThe mixture was concentrated in the stream of nitrogen
  2. dissolutionredissolved in 10 ml EtOH
  3. customThe mixture was sonicated for 5 min
  4. temperatureheated
  5. temperatureat reflux for 2 h
  6. concentrationAfter concentrating in vacuo
  7. customthe residue was partitioned between 10 ml DCM and 10 ml 2N NaOH solution
  8. customThe organic layer was separated
  9. washwashed with brine
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-3078ba92e37b45e2aa956c3ac9761e2f
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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