Diethyl Ether → HCID 21270415, compound

HRID 745959Notes

Reaction equation

HRID 745959 reaction equation
C(N([CH2:6][CH3:7])CC)C.[N:8]1([C:13]2[CH2:14][N:15]([C:18]([O:20][CH3:21])=[O:19])[CH2:16][CH:17]=2)[CH2:12][CH2:11][CH2:10][CH2:9]1.C([CH:24]([C:28](Cl)=[O:29])[C:25](Cl)=[O:26])C.CC[O:33]CC>CN(C)C1C=CN=CC=1>[C:28]([CH2:24][C:25]([C:17]1[CH2:16][N:15]([C:18]([O:20][CH3:21])=[O:19])[CH2:14][C:13]=1[N:8]1[CH2:9][CH2:10][CH2:11][CH2:12]1)=[O:26])([O:29][CH2:6][CH3:7])=[O:33]

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 8471TriethylamineHCID 109209242-Ethylpropanedioyl dichlorideHCID 21270429HCID 21270429, compound

Product 1

HCID 21270415HCID 21270415, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

Pyrrolidine (25 ml) is slowly added dropwise to a stirred suspension of 28.63 g of N-methoxycarbonyl-3-oxo-tetrahydropyrrole [prepared according to J Med Chem 5, 752 (1962)] and 29.5 g of anhydrous potassium carbonate in 200 ml ether and 100 ml toluene at 0°-5° under a nitrogen atmosphere. After 3 hours the suspension is filtered and the filtrate evaporated under reduced pressure to yield 3-pyrrolidino-N-methoxycarbonyl-2,5-dihydropyrrole as an oil. NMR (CDCl3): 4.12 (s), 4.01 (m), 3.63 (s), 3.00 (m), and 1.85 (m). Triethylamine (28 ml) and 2,4 g of 4-dimethylaminopyridine are added to a solution of 39.3 g (0.2 moles) of 3-pyrrolidino-N-methoxycarbonyl-2,5-dihydropyrrole in 850 ml of dry ether. The reaction mixture is cooled in an ice bath. A solution of 25.6 ml of ethyl malonyl chloride in 850 ml ether is added dropwise keeping the internal temperature below 5°. After 1 hour at 5° and 2 hours at room temperature, the suspension is filtered, the ether solution is washed with 10% ice cold citric acid and saturated NaHCO3 solution. The organic layer is dried over MgSO4, filtered and evaporated to yield 3-carboethoxyacetyl-4-pyrrolidino-N-methoxycarbonyl-2,5 dihydropyrrole as an oil; NMR (CDCl3) 4.44 (s), 4.37 (s), 4.17 (q) 3,73 (s), 3,42 (m), 3.32 (s), 1.90 (m) and 1.26 (t).

Workup

  1. temperatureThe reaction mixture is cooled in an ice bath
  2. customthe internal temperature below 5°
  3. filtration2 hours at room temperature, the suspension is filtered
  4. washthe ether solution is washed with 10% ice cold citric acid and saturated NaHCO3 solution
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-4dc5738231c14d2abedf64fc388d81b1
Source dataset
uspto-grants-1986_07
Patent number
US04602014

Reaction notes

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