Formaldehyde → Diethyl 1H-pyrrole-2,4-dicarboxylate

HRID 877657Notes

Reaction equation

HRID 877657 reaction equation
[N+:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[C-:2].[CH2:9]1[CH2:19][CH2:18]N2C(=NCCC2)CC1.C=[O:21].C1C[O:25][CH2:24][CH2:23]1>>[NH:1]1[CH:2]=[C:19]([C:18]([O:25][CH2:24][CH3:23])=[O:21])[CH:9]=[C:3]1[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 533707Ethyl isocyanoacetate

Product 1

HCID 12711558Diethyl 1H-pyrrole-2,4-dicarboxylateYield 26%

Conditions

Temperature
0 °C

Procedure

To a round bottom flask under argon was added ethyl 2-isocyanoacetate (100 g, 0.884 mol), dry THF (1.0 L) followed by DBU (132 g, 0.867 mol). The reaction was cooled to 0° C. and formaldehyde (16 g) was added portionwise into the reaction mixture. The reaction was then stirred at room temperature overnight. Then THF was removed under high vacuum and the residue as dissolved with water and extracted with EtOAc (2×1 L). The combined organic layer was washed with water and brine and concentrated. The residue was purified by flash silica gel column chromatography to yield 40 g (26%) of a white solid as the title compound. H1 NMR (400 MHz, CDCl3) δ ppm: 9.85 (1H, br s), 7.54 (1H, m), 7.30 (1H, m), 4.36-4.6 (4H, merging quartets), 1.37-1.26 (6H, merging triplets). LCMS (condition A): m/z=210.2 −ve.

Workup

  1. customThen THF was removed under high vacuum
  2. dissolutionthe residue as dissolved with water
  3. extractionextracted with EtOAc (2×1 L)
  4. washThe combined organic layer was washed with water and brine
  5. concentrationconcentrated
  6. customThe residue was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-11fbd9db6a15480bad372e32908916e9
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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