Diethyl Ether → 1H-Pyrrole-3-carboxylic acid, 5-(cyclohexylmethyl)-2,5-dihydro-4-hydroxy-2-oxo-, ethyl ester, (S)-

HRID 346309Notes

Reaction equation

HRID 346309 reaction equation
[O-]CC.[Na+].[CH2:5]([O:7][C:8](=[O:25])[CH2:9][C:10]([NH:12][C@@H:13]([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[C:14]([O:16]C)=O)=[O:11])[CH3:6].C(OCC)C.[Na]>C(O)C>[CH:19]1([CH2:18][C@@H:13]2[NH:12][C:10](=[O:11])[C:9]([C:8]([O:7][CH2:5][CH3:6])=[O:25])=[C:14]2[OH:16])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 14427778HCID 14427778, compound

Product 1

HCID 867434741H-Pyrrole-3-carboxylic acid, 5-(cyclohexylmethyl)-2,5-dihydro-4-hydroxy-2-oxo-, ethyl ester, (S)-Yield 99.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium ethoxide, 21 weight percent in ethanol, 204 g (0.63 mol) (5% less than theory to prevent racemization), is added to a solution of 200 g (0.67 mol) of (S)-α-[[3-ethoxy-1,3-dioxopropyl]amino]cyclohexanepropanoic acid, methyl ester in 650 ml of absolute ethanol. The solution is heated to reflux for 5 minutes, cooled and treated with about 1.5 liters of diethyl ether to precipitate the sodium salt of the product. The mixture is filtered, washed with 500 ml of diethyl ether and then with 100 ml of petroleum ether. The cake is dried on the funnel using a rubber-dam to prevent moisture from condensing to afford 178.8 g of (S)-5-(cyclohexylmethyl)-2,5-dihydro-4-hydroxy-2-oxo-1H-pyrrole-3-carboxylic acid, ethyl ester, sodium salt. The previous sodium salt is dissolved in 1 liter of water and 325 ml of 2N hydrochloric acid is added to precipitate a large taffy-like clump of material which gradually crystallizes. The clumps are broken up in a mortar and the mixture filtered, washed with water and dried to afford 143.2 g of (S)-5-(cyclohexylmethyl)-2,5-dihydro-4-hydroxy-2-oxo-1H-pyrrole-3-carboxylic acid, ethyl ester after dissolution in 10% methanol-chloroform at room temperature, charcoaling and concentration; mp 176°-180° C.; [α]D23 =-68.9° (c=1.02% methanol).

Workup

  1. temperatureThe solution is heated
  2. temperatureto reflux for 5 minutes
  3. temperaturecooled
  4. customto precipitate the sodium salt of the product
  5. filtrationThe mixture is filtered
  6. washwashed with 500 ml of diethyl ether
  7. customThe cake is dried on the funnel
  8. customfrom condensing

Sources & evidence

ORD record
ord-d0a7ab51f003401784e62ced9db50541
Source dataset
uspto-grants-1991_10
Patent number
US05061808

Reaction notes

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