Hydrochloric Acid → (S)-11,12,13,13a-tetrahydro-1-(hydroxymethyl)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 67481

Reaction equation

HRID 67481 reaction equation
[O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]2[CH:13]=[N:14][C:15]([C:16](OCC)=[O:17])=[C:5]2[C@@H:4]2[CH2:21][CH2:22][CH2:23][N:3]12.[BH4-].[Li+].Cl>O1CCCC1>[OH:17][CH2:16][C:15]1[N:14]=[CH:13][N:6]2[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:2](=[O:1])[N:3]3[CH2:23][CH2:22][CH2:21][C@H:4]3[C:5]=12

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 4148881Lithium borohydrideHCID 10041121Ethyl (7S)-12-oxo-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaene-5-carboxylate

Product 1

HCID 54004960(S)-11,12,13,13a-tetrahydro-1-(hydroxymethyl)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 46.7 g (150 mmol) of ethyl (S)-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate in 300 ml of dry tetrahydrofuran is treated dropwise at ca 35° C. with a solution of 8.3 g (377 mmol) of lithium borohydride in 110 ml of dry tetrahydrofuran. The mixture is heated to boiling under reflux for ca 40 hours, cooled to room temperature, treated with 110 ml of 12 percent hydrochloric acid and 20 ml of concentrated hydrochloric acid and again heated to boiling under reflux for 2 hours. After removal of the tetrahydrofuran in vacuo, the residue is made alkaline with concentrated ammonia. The separated material is filtered off under suction and washed with water. After recrystallisation from ethanol, there is obtained (S)-11,12,13,13a-tetrahydro-1-(hydroxymethyl)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 212°-214° C.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for ca 40 hours
  3. temperatureagain heated
  4. temperatureunder reflux for 2 hours
  5. customAfter removal of the tetrahydrofuran in vacuo
  6. filtrationThe separated material is filtered off under suction
  7. washwashed with water
  8. customAfter recrystallisation from ethanol

Sources & evidence

ORD record
ord-5e3fc2aa81114aed8da5feeb089e1190
Source dataset
uspto-grants-1982_08
Patent number
US04346034

Linked notes

Loading…