1,2-Dichloroethane → 4-methyl-5-(morpholine-4-carbonyl)-1H-pyrrole-2-carbaldehyde

HRID 1072176Notes

Reaction equation

HRID 1072176 reaction equation
[CH:1]([C:3]1[NH:7][C:6]([C:8]([OH:10])=O)=[C:5]([CH3:11])[CH:4]=1)=[O:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>CN(C=O)C.C(OCC)(=O)C>[CH3:11][C:5]1[CH:4]=[C:3]([CH:1]=[O:2])[NH:7][C:6]=1[C:8]([N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:10]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 156940785-Formyl-3-methyl-1H-pyrrole-2-carboxylic acid

Product 1

HCID 223909864-methyl-5-(morpholine-4-carbonyl)-1H-pyrrole-2-carbaldehydeYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-formyl-3-methyl-1H-pyrrole-2-carboxylic acid (306.3 mg, 2 mmol) in DMF (5 mL) was added HOBt (324.3 mg, 2.4 mmol), EDC (460.1 mg, 2.4 mmol) and then morpholine (0.21 mL, 2.4 mmol). The mixture was stirred at room temperature under nitrogen for overnight. The reaction was diluted with ethyl acetate and washed with sodium bicarbonate. The aqueous layer was extracted several times with ethyl acetate. The combined organic layer was washed with brine, dried, concentrated and column chromatographed (MeOH/DCM) to give 395 mg (89%) of 4-methyl-5-(morpholine-4-carbonyl)-1H-pyrrole-2-carbaldehyde as a light yellow foam solid. 1H NMR (360 MHz, DMSO-d6) δ 12.18 (br s, 1H, NH), 9.46 (s, 1H, CHO), 6.79 (s, 1H), 3.43 (m, 4H, 2×CH2), 2.29 (m, 4H, 2×CH2), 2.17 (s, 3H, CH3), 2.01 (s, 3H, CH3).

Workup

  1. washwashed with sodium bicarbonate
  2. extractionThe aqueous layer was extracted several times with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customcolumn chromatographed (MeOH/DCM)

Sources & evidence

ORD record
ord-3bd7ddd23770419ab9deb8aae352a710
Source dataset
uspto-grants-2005_06
Patent number
US06908930B2

Reaction notes

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