4-Methylmorpholine → tert.-butoxycarbonyl-L-tyrosyl-D-phenylalanyl-glycine benzyl ester

HRID 1759190Notes

Reaction equation

HRID 1759190 reaction equation
[CH2:1]([O:8][C:9](=[O:30])[CH2:10][NH:11][C:12](=[O:29])[C@@H:13]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[NH:14]C(OC(C)(C)C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC1C(O[C:46](=[O:64])[C@H:47]([CH2:56][C:57]2[CH:62]=[CH:61][C:60]([OH:63])=[CH:59][CH:58]=2)[NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=C(Cl)C(Cl)=C(Cl)C=1Cl>C(OCC)(=O)C.Cl>[CH2:1]([O:8][C:9](=[O:30])[CH2:10][NH:11][C:12](=[O:29])[C@@H:13]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[NH:14][C:46](=[O:64])[C@H:47]([CH2:56][C:57]1[CH:58]=[CH:59][C:60]([OH:63])=[CH:61][CH:62]=1)[NH:48][C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 79724-Methylmorpholine2×HCID 15608388Boc-L-tyrosine pentachlorophenyl esterHCID 56628183tert.-butoxycarbonyl-D-phenylalanyl-glycine benzyl ester

Product 1

HCID 57281973tert.-butoxycarbonyl-L-tyrosyl-D-phenylalanyl-glycine benzyl esterYield 90.8%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

18.55 g (45 mmoles) of the protected dipeptide ester obtained in Step 1 above are dissolved in 60 ml of ethyl acetate containing 11-15% of hydrochloric acid. After 0.5 hours of standing the solution is evaporated, and the residue is dried in a vacuum desiccator above potassium hydroxide. The resulting substance, Rf3 =0.4-0.5, is dissolved in 40 ml of dimethyl formamide, and 5.0 ml (45 mmoles) of N-methylmorpholine and 26.2 g (49.5 mmoles) of tert.-butoxycarbonyl-L-tyrosine pentachlorophenyl ester are added. The reaction mixture is stirred for 16-20 hours. During the first two hours 5.5 ml (49.5 mmoles) of N-methylmorpholine are added to the mixture in five portions. The reaction mixture is evaporated under reduced pressure, the residue is dissolved in a mixture of 300 ml of ethyl acetate and 50 ml of water, the ethyl acetate phase is separated, washed twice with 50 ml of 1 n aqueous hydrochloric acid cooled with ice water and then twice with 50 ml of water, each, dried over sodium sulfate, decolourized with carbon, filtered, and the filtrate is evaporated under reduced pressure. The crystalline residue is suspended in diisopropyl ether, the solid is filtered off, washed with diisopropyl ether, and dried in a vacuum desiccator. 23.5 g (90.8%) of tert.-butoxycarbonyl-L-tyrosyl-D-phenylalanyl-glycine benzyl ester are obtained; m.p.: 169° C., Rf10 =0.45-0.55, [α]D20 +16.3° (c=1%, in dimethyl formamide).

Workup

  1. customthe solution is evaporated
  2. dry with materialthe residue is dried in a vacuum desiccator above potassium hydroxide
  3. dissolutionThe resulting substance, Rf3 =0.4-0.5, is dissolved in 40 ml of dimethyl formamide
  4. customThe reaction mixture is evaporated under reduced pressure
  5. dissolutionthe residue is dissolved in a mixture of 300 ml of ethyl acetate and 50 ml of water
  6. customthe ethyl acetate phase is separated
  7. washwashed twice with 50 ml of 1 n aqueous hydrochloric acid
  8. temperaturecooled with ice water
  9. dry with materialtwice with 50 ml of water, each, dried over sodium sulfate
  10. filtrationfiltered
  11. customthe filtrate is evaporated under reduced pressure
  12. filtrationthe solid is filtered off
  13. washwashed with diisopropyl ether
  14. customdried in a vacuum desiccator

Sources & evidence

ORD record
ord-687ead3a75e447a18adc48ea860a57c7
Source dataset
uspto-grants-1982_07
Patent number
US04339440

Reaction notes

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