Ethylmorpholine → N-[N-(tert-butoxycarbonyl)-3-methyl-L-valyl]-3-cyclopentyl-L-alanine benzyl ester

HRID 362146Notes

Reaction equation

HRID 362146 reaction equation
[CH2:1]([O:8][C:9](=[O:25])[C@H:10]([CH2:19][CH:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1)[NH:11][C:12]([O:14]C(C)(C)C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:38]([O:42][C:43]([NH:45][C@H:46](C(O)=O)[C:47]([CH3:50])([CH3:49])[CH3:48])=[O:44])([CH3:41])([CH3:40])[CH3:39].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N1CCOCC1)C>C(#N)C.ClCCl>[CH2:1]([O:8][C:9](=[O:25])[C@H:10]([CH2:19][CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24]1)[NH:11][C:12](=[O:14])[C@H:46]([C:47]([CH3:50])([CH3:49])[CH3:48])[NH:45][C:43]([O:42][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:44])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 521998p-Toluenesulfonic acid monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734668(S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acidHCID 54072905N-(tert-butoxycarbonyl)-3-cyclopentyl-L-alanine benzyl ester

Product 1

HCID 54225868N-[N-(tert-butoxycarbonyl)-3-methyl-L-valyl]-3-cyclopentyl-L-alanine benzyl esterYield 61.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

1.54 g (4.44 mmol) of N-(tert-butoxycarbonyl)-3-cyclopentyl-L-alanine benzyl ester and 2.53 g (13.32 mmol) of 4-toluenesulphonic acid hydrate were dissolved in 20 ml of acetonitrile and the solution was left to standat room temperature for 18 hours. The white precipitate formed was filteredoff and added to a mixture of 867 mg (3.75 mmol) of N-(tert-butoxycarbonyl)-3-methyl-L-valine, 557 mg (3.64 mmol) of 1-hydroxybenzotriazole, 793 mg (4.14 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 475 mg (4.13 mmol) of N-ethylmorpholine in 25 ml of dichloromethane and stirred at room temperature for 18 hours. The solution was extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution and then driedover anhydrous magnesium sulphate. Evaporation and chromatography on silicagel using ethyl acetate/petrol (1:3) for the elution gave 1.06 g of N-[N-(tert-butoxycarbonyl)-3-methyl-L-valyl]-3-cyclopentyl-L-alanine benzyl ester as an off-white foam; MS: m/e 461 [M+H].

Workup

  1. waitthe solution was left
  2. customThe white precipitate formed
  3. extractionThe solution was extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution
  4. customEvaporation and chromatography on silicagel
  5. washfor the elution

Sources & evidence

ORD record
ord-63b511aa2dd741a7bdb1a86adc9a17b7
Source dataset
uspto-grants-1999_02
Patent number
US05866684

Reaction notes

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