4-Methylmorpholine → N-[1-(2-t-Butyloxycarbonyl-3-dibenzylaminopropyl)-1-cyclopentane-carbonyl]-O-t-butyl-(S)-tyrosine-t-butyl ester

HRID 1110460Notes

Reaction equation

HRID 1110460 reaction equation
[C:1]([O:5][C:6]([CH:8]([CH2:18][N:19]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:9][C:10]1([C:15]([OH:17])=O)[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=C[CH:42]=[CH:43][C:38]=2N=N1.[CH2:44](N=C=NCCCN(C)C)C.[C:55]([O:59][C:60](=[O:75])[C@H:61]([CH2:63][C:64]1[CH:69]=[CH:68][C:67]([OH:70])=[CH:66][C:65]=1C(C)(C)C)[NH2:62])([CH3:58])([CH3:57])[CH3:56].CN1CCOCC1>ClCCl>[C:55]([O:59][C:60](=[O:75])[C@H:61]([CH2:63][C:64]1[CH:65]=[CH:66][C:67]([O:70][C:43]([CH3:42])([CH3:38])[CH3:44])=[CH:68][CH:69]=1)[NH:62][C:15]([C:10]1([CH2:9][CH:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:18][N:19]([CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:17])([CH3:56])([CH3:57])[CH3:58]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 221554593-(1-Carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl esterHCID 573028330-t-Butyltyrosine t-butyl ester

Product 1

HCID 54036042N-[1-(2-t-Butyloxycarbonyl-3-dibenzylaminopropyl)-1-cyclopentane-carbonyl]-O-t-butyl-(S)-tyrosine-t-butyl esterYield 5,768.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice cold solution of 1-(2-t-butyloxycarbonyl-3-dibenzylaminopropyl)-1-cyclopentane carboxylic acid (12.7 g, 27 mmole) in dry dichloromethane (100 ml) was added 1-hydroxybenztriazole (4.2 g,.31 mmole), and 1-ethyl-3-(dimethylaminopropyl)-carbodiimide (7 g, 36 mmole) and the resulting solution stirred at 0° C. for 30 minutes. To this solution was added 0-t-butyltyrosine t-butyl ester (8.4 g, 28.6 mmole) and N-methylmorpholine (5.25 g, 52 mmole) and the solution allowed to stand overnight at room temperature. The solvent was evaporated under reduced pressure and the resultant mobile oil was dissolved in methylene chloride and washed with water (2 x ), 2M hydrochloric acid and saturated aqueous sodium bicarbonate (1 x) dried (MgSO4), and the solution filtered and evaporated to yield the crude product as a gum. Recrystallization from n-hexane gave the title compound as a solid (13 g, 69%), m.p. 82-87° C. A further batch of material was obtained by evaporation of the supernatant liquors and further recrystallisation. Found: C,74.12; H,8.69; N,3.87. C45H62N2O6 requires C,74.34; H,8.59; N,3.85%.

Workup

  1. waitto stand overnight at room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe resultant mobile oil was dissolved in methylene chloride
  4. washwashed with water (2 x ), 2M hydrochloric acid and saturated aqueous sodium bicarbonate (1 x)
  5. dry with materialdried (MgSO4)
  6. filtrationthe solution filtered
  7. customevaporated
  8. customto yield the crude product as a gum
  9. customRecrystallization from n-hexane

Sources & evidence

ORD record
ord-fdce5d5343454896af4d0210372ca2a1
Source dataset
uspto-grants-1990_12
Patent number
US04975444

Reaction notes

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