Diisopropylamine → Dimethyl 2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylate

HRID 1762999Notes

Reaction equation

HRID 1762999 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.Br[CH2:14][CH2:15][N:16]1[CH:20]=[CH:19][C:18]([C:21]([O:23][CH3:24])=[O:22])=[C:17]1[CH2:25][C:26]([O:28][CH3:29])=[O:27].C(NC(C)C)(C)C.[Li]>O1CCCC1.O>[CH:25]1([C:26]([O:28][CH3:29])=[O:27])[CH2:14][CH2:15][N:16]2[CH:20]=[CH:19][C:18]([C:21]([O:23][CH3:24])=[O:22])=[C:17]12

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 14479925methyl N-(2-bromoethyl)-3-methoxycarbonyl-2-pyrroleacetateHCID 45051747Lithium diisopropylamineHCID 178418339Butyllithium

Product 1

HCID 12795063Dimethyl 2,3-dihydro-1H-pyrrolizine-1,7-dicarboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

Under nitrogen, n-butyllithium (1.3M in hexane, 75 mL, 98 mmol) was added slowly at -5°-0° C., with stirring, to a solution of di(isopropyl)amine (13.8 mL, 10.0 g, 98 mmol) in tetrahydrofuran (dry, 50 mL). The resulting solution was transferred to an addition funnel and added, under nitrogen at 0°-5° C., to a stirred slurry of methyl N-(2-bromoethyl)-3-methoxycarbonyl-2-pyrroleacetate (20.0 g, 66 mmol) in tetrahydrofuran (dry, 100 mL). There was a slight temperature rise, and complete dissolution occurred after addition of about two-thirds of the lithium di(isopropyl)amine solution. The resulting solution was stirred for 2 hours while warming to 10° C., then diluted with water (100 mL) with slight heat evolution. The solvents were stripped by atmospheric distillation: 240 mL collected, with a pot temperature of 80° C., to afford a solution of dimethyl 2,3-dihydro-1H-pyrrolo-[1,2-a]pyrrole-1,7-dicarboxylate. The diester may be isolated at this point by quenching with water, extraction into an organic solvent such as ethyl acetate, and evaporation of the solvent; and purified by conventional methods. However, it is also convenient to saponify the diester to the dicarboxylic acid without isolation from the solution.

Workup

  1. customThe resulting solution was transferred to an addition funnel
  2. dissolutiona slight temperature rise, and complete dissolution
  3. distillationThe solvents were stripped by atmospheric distillation
  4. custom240 mL collected, with a pot temperature of 80° C.

Sources & evidence

ORD record
ord-c823446f003340db86d448435218eced
Source dataset
uspto-grants-1989_05
Patent number
US04835288

Reaction notes

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