Citric Acid → HCID 53668274, compound

HRID 1589323Notes

Reaction equation

HRID 1589323 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])(C)C.C([O:21][C:22](=[O:34])[C@H:23]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[NH2:24])(C)(C)C.ON1[C:40]2[CH:41]=C[CH:43]=[CH:44][C:39]=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)(O)[O-].[Na+]>CN(C=O)C.[Cl-].[Na+].O.CCCCCC.C(OCC)(=O)C.O>[CH2:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([NH:24][C@H:23]([C:22]([OH:21])=[O:34])[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=1)=[O:16])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:7])[C:4]1[CH:43]=[CH:44][CH:39]=[CH:40][CH:41]=1

Participants

13

Reactant 7

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13653351HCID 13653351, compound

Product 1

HCID 53668274HCID 53668274, compoundYield 69.5%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent2×

Procedure

To a cold (0°) solution of N-tertiarybutoxycarbonyl-L-leucine (4 g, 15.1 mM), O-methyl-L-tyrosine t-butyl ester (3.8 g, 15.1 mM) and 1-hydroxybenzotriazole (2.43 g, 15.9 mM) in DMF (30 ml) was added N-methylmorpholine (1.61 g, 15.9 mM) and N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.04 g, 15.9 mM). After stirring at 0° for 1 h the solution was allowed to warm to room temperature overnight. The reaction mixture was then concentrated in vacuo, dissolved in ethyl acetate, washed (water, 0.5 mole citric acid, brine, saturated aqueous sodium bicarbonate solution and brine), dried and evaporated in vacuo to give an oil. Chromatography on silica eluting with 25% ethyl acetate in hexane then gave the title compound as a foam (4.65 g); (Found: [m+1]+ =499.2803. C28H39N2O6 requires 499.2808); δ(CDCl3) 0.92 (6H, m, CH(CH3)3); 1.42 (9H, s, OC(CH3)3); 1.4-1.83 (3H, m, CH2CH(CH3)2); 3.03 (2H, m, CH2Tyr); 3.76 (3H, s, OCH3); 4.18 (1H, m,α-CH); 4.69 (1H, dd, J=7 and 15 Hz,α-CH); 5.12 (2H, s, CH2C6H5); 5.17 (1H, m, CONH); 6.43 (1H, m, CONH); 6.79 (2H, d, J=8 Hz, Tyr); 7.06 (2H, d, J=8 Hz, Tyr); 7.36 (5H, s, C6H5).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. dissolutiondissolved in ethyl acetate
  3. customdried
  4. customevaporated in vacuo
  5. customto give an oil

Sources & evidence

ORD record
ord-3758b4ad8fc2404b8d2188cb770f8495
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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