Hydrochloric Acid → 2-(4-fluorophenyl)-3,4-dihydro-2H-1,4-benzothiazine

HRID 5823

Reaction equation

HRID 5823 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13](=O)[NH:12][C:11]3[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=3[S:9]2)=[CH:4][CH:3]=1.[BH4-].[Na+].Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][NH:12][C:11]3[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=3[S:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 4311764Sodium borohydrideHCID 136907612-(4-Fluorophenyl)-2H-1,4-benzothiazin-3(4H)-one

Product 1

HCID 189844162-(4-fluorophenyl)-3,4-dihydro-2H-1,4-benzothiazineYield 91.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(4-fluorophenyl)-3-oxo-3,4-dihydro-2H-1,4-benzothiazine (4.0 g), sodium borohydride (2.91 g) and tetrahydrofuran (100 ml) is added dropwise with stirring boron trifluoride etherate complex (12. 5 ml) at room temperature, and the mixture is refluxed for 1.5 hour. After cooling, to the mixture is added dropwise 10% hydrochloric acid (35 ml), and the mixture is further refluxed for one hour. The reaction mixture is poured into ice water and made alkaline with potassium carbonate and extracted with ethyl acetate. The ethyl acetate layer is washed, dried and distilled to remove the solvent. The residue is recrystallized from isopropyl ether to give 2-(4-fluorophenyl)-3,4-dihydro-2H-1,4-benzothiazine (3.45 g, yield 91%) as crystals.

Workup

  1. additionis added dropwise with stirring boron trifluoride etherate complex (12. 5 ml) at room temperature
  2. temperaturethe mixture is refluxed for 1.5 hour
  3. temperatureAfter cooling, to the mixture
  4. temperaturethe mixture is further refluxed for one hour
  5. extractionextracted with ethyl acetate
  6. washThe ethyl acetate layer is washed
  7. customdried
  8. distillationdistilled
  9. customto remove the solvent
  10. customThe residue is recrystallized from isopropyl ether

Sources & evidence

ORD record
ord-ac2c06d7cbfb4525b6d01a68903c4d4b
Source dataset
uspto-grants-1993_09
Patent number
US05246929

Linked notes

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