Nordiazepam → 7-chloro-1,3-dihydro-1-[3-(2-methyl-1,3-dioxolan-2-yl)propyl]-5-phenyl-2H-1,4-benzodiazepin-2-one

HRID 1112506Notes

Reaction equation

HRID 1112506 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.Cl[CH2:21][CH2:22][CH2:23][C:24]1([CH3:29])[O:28][CH2:27][CH2:26][O:25]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:21][CH2:22][CH2:23][C:24]3([CH3:29])[O:28][CH2:27][CH2:26][O:25]3)[C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1

Participants

4

Reactant 2

HCID 2997NordiazepamHCID 800792-(3-Chloropropyl)-2-methyl-1,3-dioxolane

Product 1

HCID 203933607-chloro-1,3-dihydro-1-[3-(2-methyl-1,3-dioxolan-2-yl)propyl]-5-phenyl-2H-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

A solution of 54.2 g. of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one in 500 ml. of dimethylformamide is treated under an atomosphere of argon at 0° C. with 32.8 g. of potassium tertiary butylate and the mixture is then stirred in an ice-bath for 30 minutes. Then, at 10°-15° C. there is added a solution of 66 g. of 2-(3-chloropropyl)2-methyl-1,3-dioxolan in 100 ml. of dimethylformamide, the mixture is stirred at 20°-24° C. for 30 minutes and subsequently heated to 100° C. for 30 minutes. The mixture is cooled and poured on to 2.5 liters of ice-water. The separated oily product is extracted with methylene chloride and the organic phase washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to dryness. The residue crystallizes upon trituration with ether, and there is obtained 7-chloro-1,3-dihydro-1-[3-(2-methyl-1,3 -dioxolan-2-yl)propyl]-5-phenyl-2H-1,4-benzodiazepin-2-one having a melting point of 152°-153° C. Recrystallization from ethanol does not increase the melting point.

Workup

  1. additionThen, at 10°-15° C. there is added a solution of 66 g
  2. temperatureThe mixture is cooled
  3. extractionThe separated oily product is extracted with methylene chloride
  4. washthe organic phase washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customThe residue crystallizes upon trituration with ether

Sources & evidence

ORD record
ord-907e3cb51b6b421c9db13f464426236b
Source dataset
uspto-grants-1978_10
Patent number
US04122265

Reaction notes

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