4-Methylmorpholine → HCID 178512955, compound

HRID 67707Notes

Reaction equation

HRID 67707 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C:20]([N:22]1[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24](O)=[O:25])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[Cl:45][O:46]Cl.[NH2:48][C:49](=[NH:56])[NH:50][CH2:51][CH2:52][CH2:53][CH2:54][NH2:55].C(N(CC)CC)C>CN(C)C=O.O>[Cl:45][OH:46].[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C:20]([N:22]1[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24]([NH:55][CH2:54][CH2:53][CH2:52][CH2:51][NH:50][C:49](=[NH:48])[NH2:56])=[O:25])=[O:21])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 11899096N-[(Phenylmethoxy)carbonyl]-D-phenylalanyl-L-prolineHCID 178479707HCID 178479707, compound

Product 1

HCID 178512955HCID 178512955, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-15 °C

Procedure

4 g (10 mmoles) of benzyloxycarbonyl-D-phenylalanyl-L-proline (Nikolaides et al.: J.Med.Chem., 11, 74, 1968) are dissolved in 20 ml of dimethylformamide, cooled to -15° C., and at this temperature and constant stirring 1.11 ml (10 mmoles) of N-methyl-morpholine and 1.32 ml (10 mmoles) of chloroformic acid isobutyl ester are added. Stirring is continued for 10 minutes when the following solution is poured into it: 2.05 g (10 mmoles) of agmatine-dichlorohydrate (in formula II A means an H2N--C(NH)-- residue, B a chlorine atom and n=2) are suspended in 15 ml of dimethylformamide, 2 ml of water, then 1.4 ml (10 mmoles) of triethylamine are added, and cooled to -15° C. The reaction mixture is stirred for 2 hours at -15° C., for 1 hour without cooling, then is evaporated at reduced pressure. The evaporation residue is dissolved in 100 ml of 0.2 N hydrochloric acid and extracted three times with 20 ml of ethyl acetate. The pH of the aqueous layer is adjusted with solid sodium hydrogen carbonate to 8.0 to 8.5, and extracted five times with 20 ml of chloroform. The combined chloroform layers are washed twice with 10 ml of water, and evaporated at reduced pressure. The residue is worked up with diethyl ether, filtered, washed with diethyl ether and air-dried. Yield: 4.1 g (75 percent) of the named compound. RF3 0.5 to 0.6.

Workup

  1. additionare added
  2. additionwhen the following solution is poured into it
  3. temperaturecooled to -15° C
  4. stirringThe reaction mixture is stirred for 2 hours at -15° C., for 1 hour
  5. temperaturewithout cooling
  6. customis evaporated at reduced pressure
  7. dissolutionThe evaporation residue is dissolved in 100 ml of 0.2 N hydrochloric acid
  8. extractionextracted three times with 20 ml of ethyl acetate
  9. extractionextracted five times with 20 ml of chloroform
  10. washThe combined chloroform layers are washed twice with 10 ml of water
  11. customevaporated at reduced pressure
  12. filtrationfiltered
  13. washwashed with diethyl ether
  14. customair-dried

Sources & evidence

ORD record
ord-b5c50464a37448fa942e48da55374295
Source dataset
uspto-grants-1982_08
Patent number
US04346078

Reaction notes

Loading…