Reaction #657344

Reaction equation

methyl[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetate

NaOH

→

title compound

Yield 89.0%

[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid

Yield 89.0%

Solvents

THF

Conditions

Workup

1. 1
   Otherat RT
2. 2
   Temperaturebefore being cooled down
3. 3
   Otherquenched with 1N HCl (136 mL)
4. 4
   OtherTHF was removed under reduced pressure
5. 5
   Extractionthe aqueous layer was extracted with DCM
6. 6
   DryingThe combined organic layers were dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherThe crude solid was recrystallised in CH3CN

Procedure

To a solution of methyl[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetate (for a preparation see Intermediate 2) (28 g, 68 mmol) in THF (450 mL) at RT was added 1N NaOH (136 mL, 136 mmol). The reaction mixture was stirred at this temperature for 5 h before being cooled down and quenched with 1N HCl (136 mL). THF was removed under reduced pressure and the aqueous layer was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude solid was recrystallised in CH3CN to give the title compound (23.9 g, 89% yield) as a pale yellow powder. 1H NMR (300 MHz, CDCl3) δ7.55-7.48 (m, 2H), 7.41 (d, J=8.9 Hz, 1H), 7.38-7.31 (m, 2H), 7.22 (dd, J=2.9 and 8.9 Hz, 1H), 6.90 (d, J=2.9 Hz, 1H), 4.59 (dd, J=6.9 and 6.9 Hz, 1H), 3.81 (s, 3H), 3.70 (dd, J=6.9 and 25.7 Hz, 1H), 3.61 (dd, J=6.9 and 25.7 Hz, 1H), 2.63 (s, 3H). LC/MS: m/z 397 [M(35Cl)+H]+, Rt 2.11 min.

Source