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

HRID 850890Notes

Reaction equation

HRID 850890 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 stand at room temperature for 18 hours. The white precipitate formed was filtered off 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 dried over anhydrous magnesium sulphate. Evaporation and chromatography on silica gel 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. filtrationwas filtered off
  4. extractionThe solution was extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution
  5. dry with materialdried over anhydrous magnesium sulphate
  6. customEvaporation and chromatography on silica gel
  7. washfor the elution

Sources & evidence

ORD record
ord-ce554a03da14451381c45f5b91620ab9
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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