Acetic Acid → Urea, N-(6-chloro-5-(2-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl)-N(sup 1)-(2-hydroxyethyl)-

HRID 848148Notes

Reaction equation

HRID 848148 reaction equation
C([O:4][CH2:5][CH2:6][NH:7][C:8]([NH: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][C:24]=3[F:29])[C:15]=2[C:30]=1[Cl:31])=[O:9])(=O)C.C[O-].[Na+].C(O)(=O)C>CO>[Cl:31][C:30]1[C:15]2[C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])=[N:17][CH2:18][C:19](=[O:22])[N:20]([CH3:21])[C:14]=2[CH:13]=[CH:12][C:11]=1[NH:10][C:8]([NH:7][CH2:6][CH2:5][OH:4])=[O:9]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10942334Sodium MethoxideHCID 20562372HCID 20562372, compound

Product 1

HCID 3058274Urea, N-(6-chloro-5-(2-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl)-N(sup 1)-(2-hydroxyethyl)-

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

600 mg of 2-[3-[6-chloro-5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl]ureido]ethyl acetate dissolved in 35 ml of absolute methanol are treated with 830 mg of sodium methylate and stirred at room temperature for 1 hour. The mixture is buffered with a small amount of acetic acid and concentrated. The residue is treated with methylene chloride/10% sodium bicarbonate solution, the aqueous solution is extracted with methylene chloride and the organic solution is dried over sodium sulphate, filtered and concentrated. The residue is purified on a 30 g silica gel column with ethyl acetate/methanol (10:1) as the eluting agent and crystallised from ethanol/ether. There is obtained 1-[6-chloro-5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-3-(2-hydroxyethyl)urea which, according to the melting point, mixed melting point and IR spectrum, is identical with a sample prepared in another manner (see Example 13).

Workup

  1. concentrationconcentrated
  2. additionThe residue is treated with methylene chloride/10% sodium bicarbonate solution
  3. extractionthe aqueous solution is extracted with methylene chloride
  4. dry with materialthe organic solution is dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified on a 30 g silica gel column with ethyl acetate/methanol (10:1) as the eluting agent
  8. customcrystallised from ethanol/ether

Sources & evidence

ORD record
ord-e50216a8b88f41638f69298b09e3bccf
Source dataset
uspto-grants-1981_10
Patent number
US04294758

Reaction notes

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