Hydroxypyridinone → Trocade

HRID 565806Notes

Reaction equation

HRID 565806 reaction equation
O1CCN(CC[N+]#[C-])CC1.[C:11]([C@H:14]([C@@H:26]([CH2:35][CH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1)[C:27]([N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28])[CH2:15][N:16]1[C:20](=[O:21])[C:19]([CH3:23])([CH3:22])[N:18]([CH3:24])[C:17]1=[O:25])([OH:13])=O.[OH:41][N:42]1C=CC=CC1=O.C[Si](C)(C)ON>C(Cl)Cl>[CH:36]1([CH2:35][C@H:26]([C@@H:14]([C:11](=[O:13])[NH:42][OH:41])[CH2:15][N:16]2[C:20](=[O:21])[C:19]([CH3:23])([CH3:22])[N:18]([CH3:24])[C:17]2=[O:25])[C:27]([N:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[O:28])[CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 69975HydroxypyridinoneHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 27594344-(2-Isocyanoethyl)morpholineHCID 112701291-[2(R)-[1(R)-carboxy-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperdine

Product 1

HCID 9824350TrocadeYield 83.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.78 g of 2-morpholino-ethyl isocyanide was added at 22° to a suspension of 2.11 g of 1-[2(R)-[1(R)-carboxy-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl)piperdine from Example 11 and 0.61 g of N-hydroxy-2-pyridone in 21 ml of methylene chloride and the mixture was stirred for 3 hrs. The solution was treated with 0.58 g of O-trimethylsilyl-hydroxylamine and stirred for 2 hrs. The reaction mixture was washed with saturated NaHCO3 solution and with water and evaporated. The residue was dissolved in 20 ml of t-butyl methyl ether and 0.23 ml of water, stirred for 1½ hrs. at 22°, the suspension was diluted with 10 ml of hexane, filtered and the residue was dried at 22°/11 mbar, there being obtained 1.82 g (83%) of pure 1-[3-cyclopentyl-2(R)-[1(R)-(hydroxycarbamoyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]piperdine I, MS (EI): 436 (40%).

Workup

  1. stirringstirred for 2 hrs
  2. washThe reaction mixture was washed with saturated NaHCO3 solution and with water
  3. customevaporated
  4. dissolutionThe residue was dissolved in 20 ml of t-butyl methyl ether
  5. stirring0.23 ml of water, stirred for 1½ hrs
  6. additionat 22°, the suspension was diluted with 10 ml of hexane
  7. filtrationfiltered
  8. customthe residue was dried at 22°/11 mbar, there

Sources & evidence

ORD record
ord-e9a8e601a4734393a81ae2e3d46a640a
Source dataset
uspto-grants-2001_01
Patent number
US06172238B2

Reaction notes

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