Acetic Anhydride → 2-acetaminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine

HRID 436045Notes

Reaction equation

HRID 436045 reaction equation
C(O[C:5](=[O:7])[CH3:6])(=O)C.[NH2:8][CH2:9][CH:10]1[CH2:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])[C:13]2[CH:24]=[C:25]([Cl:28])[CH:26]=[CH:27][C:12]=2[NH:11]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[NH:8]([CH2:9][CH:10]1[CH2:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])[C:13]2[CH:24]=[C:25]([Cl:28])[CH:26]=[CH:27][C:12]=2[NH:11]1)[C:5]([CH3:6])=[O:7]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 155632447-Chloro-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-methanamine

Product 1

HCID 155632472-acetaminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

iv. 7 ml of acetic anhydride were added to a solution of 6.16 g of crude 2-aminomethyl-7-chloro-2,3-dihydro- 5-(2-fluorophenyl)-1H-1,4-benzodiazepine in 200 ml of methylene chloride. The solution was layered with 200 ml of saturated aqueous sodium bicarbonate and the mixture was stirred for 20 minutes. The organic layer was separated, washed with sodium bicarbonate solution, dried over sodium sulphate and evaporated to leave 6.2 g of resinous 2-acetaminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine. This material was heated with 40 g of polyphosphoric acid at 150°C for 10 minutes. The cooled mixture was dissolved in water, made alkaline with ammonia and ice and extracted with methylene chloride. The extracts were dried and evaporated and the residue (5.7 g) was chromatographed over 120 g of silica gel using 20% methanol in methylene chloride. The clear fractions were combined and evaporated to yield resinous 8-chloro-3a,4-dihydro-6-(2-fluorophenyl)-1-methyl-4H-imidazo-[1,5-a][1,4]benzodiazepine. A mixture of this material with 500 ml of toluene and 30 g of manganese dioxide was heated to reflux for 1.5 hours. The manganese dioxide was separated by filtration over Celite. The filtrate was evaporated and the residue crystallised from diethyl ether to yield 8-chloro-6-(2-fluorophenyl)-1-metnhyl-4H-imidazo[1,5-a][1,4]benzodiazepine of melting point 152°-154° C. An analytical sample was recrystallised from methylene chloride/hexane.

Workup

  1. customThe organic layer was separated
  2. washwashed with sodium bicarbonate solution
  3. dry with materialdried over sodium sulphate
  4. customevaporated

Sources & evidence

ORD record
ord-b9f5156920c6492e888c6947aacc1331
Source dataset
uspto-grants-1977_02
Patent number
US04007219

Reaction notes

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