p-Toluenesulfonic acid monohydrate → Flubromazepam Isomer

HRID 1034411Notes

Reaction equation

HRID 1034411 reaction equation
C[O:2][C:3](=O)[CH2:4]/[N:5]=[C:6](/[C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[NH2:21])\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Br:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:6]1[C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[NH:21][C:3](=[O:2])[CH2:4][N:5]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 178501583HCID 178501583, compound

Product 1

HCID 15292433Flubromazepam IsomerYield 83.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 72.7 g (0.199 moles) of (Z)-N-[(2-amino-5-fluorophenyl)(2-bromophenyl)methylene]glycine methyl ester), 1450 mL of toluene, and 42.8 g (0.225 moles) of p-toluenesulfonic acid monohydrate was heated to reflux for 3 hours under nitrogen After cooling, the product crystallized out of the reaction mixture The resultant suspension was filtered and the collected solid was washed twice with 100 mL of toluene, followed by two washes with 100 mL of hexane. The solid was partitioned between 1.0 L of methylene chloride and 1.0 L of saturated NaHCO3 solution. The organic layer was separated and the aqueous layer was extracted with 250 mL of methylene chloride. The combined organic layers were washed twice with 250 mL of 1:1 mixture brine/water, dried with Na2SO4, filtered, and concentrated under vacuum. The residue was redissolved in 800 mL of methylene chloride and concentrated to give 55.5 g of 5-(2-bromophenyl)-7-fluoro-1,3-dihydro-1,4-benzodiazepine-2 (2H)-one as a light yellow solid.

Workup

  1. temperatureto reflux for 3 hours under nitrogen
  2. temperatureAfter cooling
  3. customthe product crystallized out of the reaction mixture The resultant suspension
  4. filtrationwas filtered
  5. washthe collected solid was washed twice with 100 mL of toluene
  6. customThe solid was partitioned between 1.0 L of methylene chloride and 1.0 L of saturated NaHCO3 solution
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with 250 mL of methylene chloride
  9. washThe combined organic layers were washed twice with 250 mL of 1:1 mixture brine/water
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum
  13. dissolutionThe residue was redissolved in 800 mL of methylene chloride
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-54a8faef19714293a15d35237aeaeec9
Source dataset
uspto-grants-1994_05
Patent number
US05317018

Reaction notes

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