4-Methylmorpholine → HCID 22816335, compound

HRID 1680582Notes

Reaction equation

HRID 1680582 reaction equation
[C:1]([NH:8][CH2:9][C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[NH2:28][C@H:29]([C:37]([CH:39]1[CH:46]2[CH2:47][CH:42]3[CH2:43][CH:44]([CH2:48][C:40]1([NH2:49])[CH2:41]3)[CH2:45]2)=[O:38])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[C:1]([NH:8][CH2:9][C:10]([NH:28][C@H:29]([C:37]([CH:39]1[CH:46]2[CH2:47][CH:42]3[CH2:43][CH:44]([CH2:48][C:40]1([NH2:49])[CH2:41]3)[CH2:45]2)=[O:38])[CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:12])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 78288N-(tert-butoxycarbonyl)glycineHCID 22816346HCID 22816346, compound

Product 1

HCID 22816335HCID 22816335, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 1.42 g of Boc-glycine and 0.90 ml of N-methylmorpholine in 10 ml of dry methylene chloride under nitrogen is allowed to react with 1.05 ml of isobutylchloroformate at -45° C. The reaction mixture is allowed to warm to -20° C. then recooled to -40° C. To this solution is added 2.38 g of L-phenylalanyl-1-aminoadamantane. The cooling bath is removed and the reaction mixture is allowed to stand overnight at room temperature. The reaction mixture is filtered, diluted with 20 ml of methylene chloride and washed with 10 ml of cold 1 M potassium bisulfate solution followed by washing with 10 ml of cold 2 M potassium carbonate solution and 10 ml of saturated sodium chloride solution. The reaction mixture is dried over sodium sulfate, filtered and concentrated. The product separates as crystals upon addition of ether. The crystalline material is collected to give Boc-glycyl-L-phenylalanyl-1-aminoadamantane. A dry solution of 2.8 g of Boc-glycol-L-phenylalanyl-1-aminoadamantane in 15 ml of methylene chloride under a nitrogen atmosphere at 5° C. is allowed to react with 10 ml of trifluoroacetic acid. The reaction mixture is allowed to stand for 30 minutes at room temperature. The solution is concentrated under reduced pressure then diluted with 10 ml of 5 M potassium carbonate solution and extracted with methylene chloride. The reaction mixture is dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure to give glycyl-L-phenylalanyl-1-aminoadamantane which is represented by the following formula ##STR37##

Workup

  1. customthen recooled to -40° C
  2. customThe cooling bath is removed
  3. filtrationThe reaction mixture is filtered
  4. additiondiluted with 20 ml of methylene chloride
  5. washwashed with 10 ml of cold 1 M potassium bisulfate solution
  6. washby washing with 10 ml of cold 2 M potassium carbonate solution and 10 ml of saturated sodium chloride solution
  7. dry with materialThe reaction mixture is dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe product separates as crystals upon addition of ether
  11. customThe crystalline material is collected

Sources & evidence

ORD record
ord-a1ec414f930d4d3da70725fd70b4f2cf
Source dataset
uspto-grants-1981_06
Patent number
US04273704

Reaction notes

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