4-Methylmorpholine → N'-[4-(carbobenzoxyglycylamino)-phenyl]-N,N-dimethylacetamidine

HRID 461884Notes

Reaction equation

HRID 461884 reaction equation
C(OC(Cl)=O)C.[C:7]([NH:17][CH2:18][C:19]([OH:21])=O)([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].CN1CCOCC1.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]=[C:37]([N:39]([CH3:41])[CH3:40])[CH3:38])=[CH:32][CH:31]=1>O1CCCC1>[C:7]([NH:17][CH2:18][C:19]([NH:29][C:30]1[CH:31]=[CH:32][C:33]([N:36]=[C:37]([N:39]([CH3:40])[CH3:41])[CH3:38])=[CH:34][CH:35]=1)=[O:21])([O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:8]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 14349BenzyloxycarbonylglycineHCID 169706N'-(4-Aminophenyl)-N,N-dimethylacetamidine

Product 1

HCID 21392883N'-[4-(carbobenzoxyglycylamino)-phenyl]-N,N-dimethylacetamidineYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

22.8 g (0.21 mol) of chloroformic acid ethyl ester were added dropwise at -15° C to a solution of 41.8 g (0.2 mol) of N-(carbobenzoxy)-glycine and 21.3 g (0.21 mol) of N-methylmorpholine in 250 ml of absolute tetrahydrofuran. The mixture was stirred for 10 minutes at -10° C and was then filtered. A solution of 33.7 g (0.19 mol) of N'-(4-aminophenyl)-N,N-dimethylacetamidine in 100 ml of absolute tetrahydrofuran was added dropwise to the filtrate at -10° C. The mixture was then stirred for 30 minutes at -10° C, 1 hour at 0° C and 2 hours at room temperature. Thereafter, the mixture was concentrated on a rotary evaporator, suspended in sodium hydroxide solution and repeatedly extracted with chloroform. The chloroform phase was dried with Na2SO4 and concentrated. The residue was recrystallized from benzene-ligroin. 39.2 g of N'-[4-(carbobenzoxyglycylamino)-phenyl]-N,N-dimethylacetamidine of melting point 133° C were thus obtained and were slowly introduced into 800 ml of HBr/glacial acetic acid, with cooling. The mixture was stirred for 2 hours at room temperature and was then stirred into 2 liters of dry ether. A crystalline precipitate formed and this was filtered off, washed with ether and then dissolved in water. The aqueous solution was rendered alkaline, with cooling, and was repeatedly extracted with chloroform. The organic extracts were dried over Na2SO4 and concentrated in vacuo. The residue was recrystallized from toluene to afford 22.9 g (51% of theory) of N,N-dimethyl-N'-(4-glycylaminophenyl)acetamidine, melting point 142°-145° C.

Workup

  1. filtrationwas then filtered
  2. stirringThe mixture was then stirred for 30 minutes at -10° C, 1 hour at 0° C and 2 hours at room temperature
  3. concentrationThereafter, the mixture was concentrated on a rotary evaporator
  4. extractionrepeatedly extracted with chloroform
  5. dry with materialThe chloroform phase was dried with Na2SO4
  6. concentrationconcentrated
  7. customThe residue was recrystallized from benzene-ligroin

Sources & evidence

ORD record
ord-ddaa8843e2d04eb1a30199e006706bff
Source dataset
uspto-grants-1977_12
Patent number
US04064270

Reaction notes

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