Trifluoroacetic acid → HCID 70567604, compound

HRID 1680593Notes

Reaction equation

HRID 1680593 reaction equation
C([NH:8][C@H:9]([C:17]([C:19]1([NH2:33])[CH:26]2[CH2:27][CH:22]3[CH2:23][CH:24]([CH2:28][C:20]1([C:29]([O:31][CH3:32])=[O:30])[CH2:21]3)[CH2:25]2)=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(OC(C)(C)C)=O.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:8][C@H:9]([C:17]([C:19]1([NH2:33])[CH:26]2[CH2:25][CH:24]3[CH2:23][CH:22]([CH2:21][C:20]1([C:29]([O:31][CH3:32])=[O:30])[CH2:28]3)[CH2:27]2)=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 70565002HCID 70565002, compound

Product 1

HCID 70567604HCID 70567604, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1.7 g of methyl Boc-L-phenylalanyl-2-amino-1-adamantanecarboxylate (Isomer B) in 10 ml of methylene chloride is added 5 ml of trifluoroacetic acid. After 15 minutes the reaction mixture is concentrated to a small volume under a stream of nitrogen then distributed between 25 ml of methylene chloride and 5 ml of 5 M potassium carbonate solution. The methylene chloride layer is collected and the aqueous phase is extracted with another 25 ml of methylene chloride. The methylene chloride extracts are combined, dried over sodium sulfate and concentrated to a small volume, then diluted with hexane. The crystalline product which forms is collected by filtration to give methyl L-phenylalanyl-2-amino-1-adamantanecarboxylate (Isomer B) melting at 88°-90° C. The mixed anhydride from 1.65 g of Boc-L-tyrosyl-D-methionylglycine is prepared as in Part A above. To it is added 1.256 g of methyl L-phenylalanyl-2-amino-1-adamantanecarboxylate (Isomer B). The reaction is allowed to proceed for 1 hour at room temperature then 50 ml of methylene chloride is added. The reaction mixture is filtered, washed with 10 ml portions of 2 M potassium carbonate solution and 1 M potassium bisulfate solution, dried over sodium sulfate, and filtered. The solvent is removed under vacuum to give a glass which is methyl Boc-L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl-2-amino-1-adamantanecarboxylate. This product is dissolved in 10 ml of glacial acetic acid and 20 ml of a 5 N solution of hydrogen chloride in dioxane is added. The reaction is allowed to proceed for 45 minutes, then the reaction mixture is concentrated under reduced pressure. The residue is dissolved in aqueous methanol and filtered through Filter Cel, then extracted with six 10 ml portions of methylene chloride and ethyl acetate. The ethyl acetate extracts are combined and the solvent is removed by evaporation. The residue is dissolved in 40 ml of water, filtered through Filter Cel and lyophilized to give the product methyl L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl 2-amino-1-adamantanecarboxylate hydrochloride which is represented by the following formula ##STR48##

Workup

  1. concentrationAfter 15 minutes the reaction mixture is concentrated to a small volume under a stream of nitrogen
  2. customThe methylene chloride layer is collected
  3. extractionthe aqueous phase is extracted with another 25 ml of methylene chloride
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to a small volume
  6. additiondiluted with hexane
  7. filtrationThe crystalline product which forms is collected by filtration

Sources & evidence

ORD record
ord-a9f6757636ee44beb3c19d8a359b4081
Source dataset
uspto-grants-1981_06
Patent number
US04273704

Reaction notes

Loading…