1-Bromo-3-chloropropane → 7-(3-Chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

HRID 2196056Notes

Reaction equation

HRID 2196056 reaction equation
[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:4]1=2)[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:27][CH2:28][CH2:29][Cl:30]>O.C(#N)C>[Cl:30][CH2:29][CH2:28][CH2:27][O:19][C:16]1[CH:17]=[CH:18][C:4]2[N:3]([CH2:1][CH3:2])[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]=2[CH:15]=1

Participants

6

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 686733851-Ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 686732537-(3-Chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dioneYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

1-Ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.85 g, 7.1 mmol) and potassium carbonate (1.2 g, 8.5 mmol) were added to 50% water-containing acetonitrile (40 ml), and dissolved by heating to 70° C. 1-Bromo-3-chloropropane (2.1 ml, 21 mmol) was added thereto, and heating was conducted under reflux for 6 hours. The reaction mixture was cooled to room temperature. Water was added, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 2.18 g (yield: 91%) of 7-(3-chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione as a colorless oil.

Workup

  1. dissolutiondissolved
  2. temperatureheating
  3. temperatureunder reflux for 6 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionextraction with ethyl acetate
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:1)
  9. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-a821b6c20fa44ff9a97c2763b10ba923
Source dataset
uspto-grants-2012_12
Patent number
US08338406B2

Reaction notes

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