Ethyl allyl(2-oxoethyl)carbamate → Ethyl 1-[(R)-1-Phenylethyl]hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate

HRID 12942Notes

Reaction equation

HRID 12942 reaction equation
[C:1]1([C@H:7]([NH:9][CH2:10]C(O)=O)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([O:16][C:17](=[O:25])[N:18]([CH2:22][CH:23]=[CH2:24])[CH2:19][CH:20]=O)[CH3:15]>C1(C)C=CC=CC=1.CO>[C:1]1([C@H:7]([N:9]2[CH:20]3[CH2:19][N:18]([C:17]([O:16][CH2:14][CH3:15])=[O:25])[CH2:22][CH:23]3[CH2:24][CH2:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 11084330Ethyl allyl(2-oxoethyl)carbamateHCID 28897015N-((1R)-1-Phenylethyl)glycine

Product 1

HCID 66758144Ethyl 1-[(R)-1-Phenylethyl]hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of (1-(R)-phenyl-ethylamino)-acetic acid (25.6 g) in 384 mL of toluene was heated to 90° C. To this 170 g (1.1 equivalents) of a 15.84 wt. % solution of allyl-(2-oxo-ethyl)-carbamic acid ethyl ester (U.S. Pat. No. 5,071,999) in toluene, was added over 20 minutes and the mixture was stirred at 90° C. for 14 hours then at 95° C. for 12 hours. After cooling, the product was extracted with 2×115 g of 20% citric acid solution. The citric acid solution was diluted with 205 mL of isopropyl acetate, and the mixture was neutralized with a solution of 51.2 g K2CO3 in 120 g water, and thoroughly shaken. The layers were separated, and the aqueous layer was extracted again with 102 mL of isopropyl acetate. The organic extracts were combined and distilled under reduced pressure to provide an oil which was then diluted with 125 mL of methanol to provide 140 g (100% yield) of the title compound as a 30% by weight solution in methanol.

Workup

  1. waitat 95° C. for 12 hours
  2. temperatureAfter cooling
  3. extractionthe product was extracted with 2×115 g of 20% citric acid solution
  4. additionThe citric acid solution was diluted with 205 mL of isopropyl acetate
  5. stirringthoroughly shaken
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted again with 102 mL of isopropyl acetate
  8. distillationdistilled under reduced pressure
  9. customto provide an oil which

Sources & evidence

ORD record
ord-bbd0e987fa5f4e2e8a3437b43767ad72
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Reaction notes

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