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

HRID 429524Notes

Reaction equation

HRID 429524 reaction equation
C(N1C[CH2:7][O:6]CC1)C.O.ON1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2N=N1.C([N:22]=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]>C(Cl)Cl>[CH2:7]([O:6][NH:22][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]([CH3:42])([CH3:43])[N:38]([CH3:44])[C:37]1=[O:45])=[O:32])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 7525Ethylmorpholine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 112701291-[2(R)-[1(R)-carboxy-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperdine

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-ethyhnorpholine, 0.60 g of N-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]piperidine (IX) from Example 5 or 6 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-benzylhydroxylamme hydrochloride and then 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, 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-41293cbffe5c43309f62dcf36671dbb0
Source dataset
uspto-grants-2001_11
Patent number
US06316633B1

Reaction notes

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