Diazepam → 7-chloro-1-methyl-5-phenyl-2-trimethylsiloxy-1H-1,4-benzodiazepine

HRID 2058290Notes

Reaction equation

HRID 2058290 reaction equation
C[Li].C(NC(C)C)(C)C.[Cl:10][C:11]1[CH:12]=[CH:13][C:14]2[N:20]([CH3:21])[C:19](=[O:22])[CH2:18][N:17]=[C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:15]=2[CH:29]=1.[CH3:30][Si:31]([CH3:34])([CH3:33])Cl>C(OCC)C.O1CCCC1>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]2[N:20]([CH3:21])[C:19]([O:22][Si:31]([CH3:34])([CH3:33])[CH3:30])=[CH:18][N:17]=[C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:15]=2[CH:29]=1

Participants

7

Reactant 4

HCID 3016DiazepamHCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 178418348HCID 178418348, compound

Product 1

HCID 126021197-chloro-1-methyl-5-phenyl-2-trimethylsiloxy-1H-1,4-benzodiazepineYield 95.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of methyllithium in diethyl ether (0.0275 mol, 15.3 ml of 1.8 M solution) was added dropwise to a solution of 3.04 g (0.03 mol) of diisopropylamine in 25 ml of diethyl ether. The reaction mixture was cooled to -70° C. and a solution of 7.12 g (0.025 mol) of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one in 40 ml of tetrahydrofuran was added dropwise. The reaction mixture became dark red. Trimethylchlorosilane (11.4 ml; 0.09 mol) was added dropwise, after which the reaction mixture was warmed to room temperature, stirred for 3 hours and then filtered. The filtrate was evaporated to dryness and the residue was dissolved in 150 ml of trichlorofluoromethane. This solution was filtered to remove undissolved solid; the filtrate was evaporated to dryness under reduced pressure to give 8.52 g of 7-chloro-1-methyl-5-phenyl-2-trimethylsiloxy-1H-1,4-benzodiazepine as a light orange glass: 1H NMR (CCl3F) δ 0.0 ppm (s, 9H), 2.62 ppm (s, 3H), 5.76 ppm (s, 1H) and 6.4-7.6 ppm (m, 8H).

Workup

  1. temperatureafter which the reaction mixture was warmed to room temperature
  2. filtrationfiltered
  3. customThe filtrate was evaporated to dryness
  4. dissolutionthe residue was dissolved in 150 ml of trichlorofluoromethane
  5. filtrationThis solution was filtered
  6. customto remove undissolved solid
  7. customthe filtrate was evaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-acb68992f4bc46a7aa846f60c50e1c10
Source dataset
uspto-grants-1980_07
Patent number
US04215044

Reaction notes

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