Ethylmorpholine → 1-[2(R)-[1(R)-(benzyloxycarbamoyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperidine

HRID 565803

Reaction equation

HRID 565803 reaction equation
C(N1CCOCC1)C.O.OC1C2N=NNC=2C=CC=1.C(N=C=NCCCN(C)C)C.[C:31]([C@H:34]([C@@H:46]([CH2:55][CH:56]1[CH2:60][CH2:59][CH2:58][CH2:57]1)[C:47]([N:49]1[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]1)=[O:48])[CH2:35][N:36]1[C:40](=[O:41])[C:39]([CH3:43])([CH3:42])[N:38]([CH3:44])[C:37]1=[O:45])(O)=[O:32].Cl.[CH2:62]([O:69][NH2:70])[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1>C(Cl)Cl>[CH2:62]([O:69][NH:70][C:31]([C@H:34]([C@@H:46]([CH2:55][CH:56]1[CH2:57][CH2:58][CH2:59][CH2:60]1)[C:47]([N:49]1[CH2:50][CH2:51][CH2:52][CH2:53][CH2:54]1)=[O:48])[CH2:35][N:36]1[C:40](=[O:41])[C:39]([CH3:43])([CH3:42])[N:38]([CH3:44])[C:37]1=[O:45])=[O:32])[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1

Participants

7

Reactant 5

HCID 7525Ethylmorpholine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 102312Benzyloxyamine hydrochlorideHCID 112701291-[2(R)-[1(R)-carboxy-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperdineHCID 178526939HCID 178526939, compound

Product 1

HCID 543913361-[2(R)-[1(R)-(benzyloxycarbamoyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperidineYield 73.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.74 g of N-ethylmorpholine, 0.60 g of hydroxybenzotriazole hydrate and 0.75 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide were added at 0° in succession to a solution of 1.38 g of 1-[2(R)-[1(R)-carboxy-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperdine VI in 13 ml of methylene chloride and the mixture was stirred at 0° for 20 min. The reaction mixture was treated with 0.45 g of N-ethylmorpholine and 0.63 g of O-benzylhydroxylamine hydrochloride and stirred at 0° for 30 min. and at 22° for 17 hrs. The solution was diluted with 13 ml of methylene chloride, washed with sodium bicarbonate solution and dilute hydrochloric acid, dried and concentrated. The residue was crystallized from ethyl acetate/hexane and the crystallizate was dried, there being obtained 1.26 g (73%) of pure 1-[2(R)-[1-(R)-(benzyloxycarbamoyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperidine VII, m.p. 138-140°.

Workup

  1. stirringstirred at 0° for 30 min. and at 22° for 17 hrs
  2. washwashed with sodium bicarbonate solution and dilute hydrochloric acid
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was crystallized from ethyl acetate/hexane
  6. customthe crystallizate was dried

Sources & evidence

ORD record
ord-25099202120246019c94bc32a7970c73
Source dataset
uspto-grants-2001_01
Patent number
US06172238B2

Linked notes

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