Reaction #657345

Reaction equation

Et3N

methyl[(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-thioxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetate

AcCl

hydrazine monohydrate

→

crude title compound

Yield 100.0%

Methyl[(3S)-2-[2-acetylhydrazino]-5-(4-chlorophenyl)-7-(methyloxy)-3H-1,4-benzodiazepin-3-yl]acetate

Yield 100.0%

Solvents

THF

Conditions

Workup

1. 1
   Otherat 0° C.
2. 2
   Temperatureto warm to RT
3. 3
   workup.STIRRINGstir for 1 h
4. 4
   Otherthen quenched with water
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   ExtractionThe resulting aqueous layer was then extracted with DCM
7. 7
   Dryingthe organic layer was dried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo

Procedure

To a suspension of methyl[(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-thioxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetate (for a preparation see Intermediate 4) (30.2 g, 77.7 mmol) in THF (800 mL) at 0° C. was added hydrazine monohydrate (11.3 mL, 233 mmol) dropwise. The reaction mixture was stirred for 4 h between 0° C. and 15° C. before being cooled at 0° C. Et3N (32.4 mL, 230 mmol) was then added slowly and AcCl (16.3 mL, 230 mmol) was added dropwise. The mixture was allowed to warm to RT and stir for 1 h then quenched with water and concentrated under reduced pressure. The resulting aqueous layer was then extracted with DCM and the organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the crude title compound (34 g, 100% yield) which was used without further purification. LC/MS: m/z 429 [M(35Cl)+H]+, Rt 2.83 min.

Source