1,2-Dichloroethane → HCID 86594170, compound

HRID 33217Notes

Reaction equation

HRID 33217 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[CH:15]=[CH:16][C:17]([C:19]#[N:20])=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].[CH2:23](N)[C:24]#[CH:25].C(Cl)CCl.C1C=CC2N([OH:40])N=NC=2C=1.C([O-])(O)=O.[Na+]>CCO.O.ClCCl>[CH2:23]([NH:20][C:19]([C:17]1[CH:16]=[CH:15][C:12]2[CH2:13][CH2:14][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10][C:11]=2[CH:18]=1)=[O:40])[C:24]#[CH:25]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 14797Potassium HydroxideHCID 757711-HydroxybenzotriazoleHCID 239041PropargylamineHCID 516892Sodium BicarbonateHCID 18173275tert-Butyl 7-cyano-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate

Product 1

HCID 86594170HCID 86594170, compoundYield 781.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(tert-butyloxycarbonyl)-7-cyano-2,3,4,5-tetrahydro-1H-3-benzazepine (10 g, 37 mmol) and KOH (4.1 g, 73 mmol) in EtOH (100 ml) and water (20 ml) was heated under reflux for 24 h. Mixture allowed to cool and evaporated in vacuo and the residue redissolved in water (150 ml). The solution was acidified to pH4 and the precipitate filtered and dried. The crude acid (5 g, 17 mmol) was then dissolved in dichloromethane (100 ml), under Argon and propargylamine (0.77 g, 14 mmol), EDC (2.9 g 15 mmol) and HOBT (200 mg) added and the reaction stirred for 18 h. Saturated NaHCO3 solution (100 ml) was added and the organic layer separated. The aqueous layer was re-extracted with dichloromethane and the combined organic layers dried and evaporated in vacuo. The residue was purified by silica gel chromatography (gradient elution, hexane/ethyl acetate) to give the title compound (3.8 g) as a colourless solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 h
  3. temperatureto cool
  4. customevaporated in vacuo
  5. dissolutionthe residue redissolved in water (150 ml)
  6. filtrationthe precipitate filtered
  7. customdried
  8. customthe organic layer separated
  9. extractionThe aqueous layer was re-extracted with dichloromethane
  10. customthe combined organic layers dried
  11. customevaporated in vacuo
  12. customThe residue was purified by silica gel chromatography (gradient elution, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c37243df2ac64e0dba7f7e798d323a00
Source dataset
uspto-grants-2008_09
Patent number
US07429579B2

Reaction notes

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