Dichloromethane → 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one

HRID 1055821Notes

Reaction equation

HRID 1055821 reaction equation
OC(C(F)(F)F)=O.[NH2:8][CH2:9][C:10]1[NH:11][CH:12]=[CH:13][C:14]=1[C:15]([OH:17])=O.C(Cl)Cl.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CCOC(C)=O>[NH:11]1[CH:12]=[CH:13][C:14]2[C:15](=[O:17])[NH:8][CH2:9][C:10]1=2

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 1317364112-(aminomethyl)-1H-pyrrole-3-carboxylic acid TFA salt

Product 1

HCID 694035305,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-oneYield 31.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 5 L round-bottomed flask was charged with 2-(aminomethyl)-1H-pyrrole-3-carboxylic acid TFA salt (1.02 Kg, 2.7 mol), DCM (3.2 L), and DIPEA (2.75 Kg, 21.3 mol). To the reaction mixture was added (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (1.55 Kg, 2.97 mol, Accela ChemBio Co. Ltd) and stirred at RT overnight. The solvent was removed in vacuo. The crude material was purified by column chromatography on silica gel (eluting with a gradient of 0% to 5% NH3 (2M in MeOH)/DCM) to give crude product 510 g as sticky oil. The crude product was diluted with EtOAc (4.5 L) and stirred for 1 h. The resulting precipitate was collected by filtration and dried to afford 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (104 g, 31% yield) as a white solid. The filtrate was concentrated and re-purified by column chromatography on silica gel to give more product 46.5 g (13.6% yield) as a white solid. Overall 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (150.5 g, 44.6% yield) was obtained. MS (ESI, pos. ion) m/z: 123 (M+1); 1H NMR (400 MHz, MeOD) δ 6.87 (d, J=3.2 Hz, 1H), 6.27 (d, J=3.2 Hz, 1H), 4.27 (s, 2H).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe crude material was purified by column chromatography on silica gel (
  3. washeluting with a gradient of 0% to 5% NH3 (2M in MeOH)/DCM)
  4. customto give crude product 510 g as sticky oil
  5. stirringstirred for 1 h
  6. filtrationThe resulting precipitate was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-07d4eb527bf0472398b02b33061242a1
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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