Trifluoroacetic acid → HCID 70567604, compound

HRID 1680592Notes

Reaction equation

HRID 1680592 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 1.862 g of methyl Boc-L-phenylalanyl-2-amino-1-adamantanecarboxylate (Isomer A) in 10 ml of methylene chloride is added 5 ml of trifluoracetic acid. After 15 minutes at room temperature the reaction mixture is concentrated to a small volume and 5 ml of cold potassium carbonate is added. The mixture is extracted twice with 20 ml of chloroform. The combined chloroform extracts are dried over sodium sulfate to give methyl L-phenylalanyl-2-amino-1-adamantanecarboxylate (Isomer A) as a crystalline solid melting at 160°-167° C. Under a nitrogen atmosphere at -50° C. a dry (1 g of 4 A sieves) solution of 1.878 g of Boc-L-tyrosyl-D-methionyl-glycine and 0.444 ml of N-methylmorpholine in 25 ml of tetrahydrofuran is stirred while 0.52 ml of isobutylchloroformate is added. The reaction mixture is allowed to warm to -10° C. for 10 minutes then cooled to -40° C. and 1.24 g of methyl L-phenylalanyl- 2-amino-1-adamantanecarboxylate is added. The reaction mixture is stirred overnight at room temperature. Upon the addition of water a solid separates and is collected by filtration, washed and dried. The residue is dissolved in methanol, filtered through Filter Cel, concentrated and diluted with equal volumes of ethyl acetate and ether. The solid which precipitates is collected by filtration, washed with ether and dried to give methyl Boc-L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl-2-amino-1-adamantanecarboxylate (Isomer A). 2.34 Grams of this compound is dissolved in 10 ml of acetic acid and 20 ml of a 5 N solution of hydrogen chloride in dioxane is added. The reaction mixture is concentrated under a stream of nitrogen for 11/2 hours and diluted with 150 ml of ether. The solid which forms is collected, dissolved in methanol, concentrated to about 10 ml and diluted with 40 ml of water then allowed to stand overnight at room temperature. The solution is filtered and lyophilized to give methyl L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl-2-amino-1-adamantanecarboxylate hydrochloride (Isomer A) which is represented by the following formula ##STR47##

Workup

  1. concentrationAfter 15 minutes at room temperature the reaction mixture is concentrated to a small volume and 5 ml of cold potassium carbonate
  2. additionis added
  3. extractionThe mixture is extracted twice with 20 ml of chloroform
  4. dry with materialThe combined chloroform extracts are dried over sodium sulfate

Sources & evidence

ORD record
ord-9d653b7b962a437a8f5832c11db58bb2
Source dataset
uspto-grants-1981_06
Patent number
US04273704

Reaction notes

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