Sodium Hydroxide → HCID 67173666, compound

HRID 570162Notes

Reaction equation

HRID 570162 reaction equation
C[O:2][C:3](=[O:29])[CH2:4][C@@H:5]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:8]=2[N:7]2[C:25]([CH3:28])=[N:26][N:27]=[C:6]12.[OH-].[Na+]>C1COCC1>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[C:9]3[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:8]=3[N:7]3[C:25]([CH3:28])=[N:26][N:27]=[C:6]3[C@H:5]([CH2:4][C:3]([OH:29])=[O:2])[N:11]=2)=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 52936135HCID 52936135, compound

Product 1

HCID 67173666HCID 67173666, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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.

Workup

  1. customat RT
  2. temperaturebefore being cooled down
  3. customquenched with 1N HCl (136 mL)
  4. customTHF was removed under reduced pressure
  5. extractionthe aqueous layer was extracted with DCM
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude solid was recrystallised in CH3CN

Sources & evidence

ORD record
ord-da75f2a1155842b28855126852ef5dcf
Source dataset
uspto-grants-2015_05
Patent number
US09023842B2

Reaction notes

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