Tetrahydrofuran → 4-(4-hydroxy-piperidin-1-ylmethyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde

HRID 1839667Notes

Reaction equation

HRID 1839667 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1[CH:8]=[O:9].[CH2:10]1C[O:13][CH2:12][CH2:11]1>O.C(O)(=O)C.C=O>[OH:13][CH:12]1[CH2:11][CH2:10][N:4]([CH2:5][C:6]2[C:2]([CH3:1])=[C:3]([CH:8]=[O:9])[NH:4][C:5]=2[CH3:7])[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 8028TetrahydrofuranHCID 2704653,5-Dimethyl-1H-pyrrole-2-carbaldehyde

Product 1

HCID 225618614-(4-hydroxy-piperidin-1-ylmethyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehydeYield 49%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 712FormaldehydeSolventHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 3,5-dimethyl-1H-pyrrole-2-carbaldehyde (2.5 g, 20 mmol) in THF (40 mL), water (20 mL), acetic acid (3 mL), formaldehyde (37% wt. % solution in water, 5 mL) and the appropriate amine (30 mL) was heated to reflux (oil bath 90-100° C.) for 6 hours and then stirred at rt for overnight. The reaction was concentrated to a volume of 30 mL, basified with 2N NaOH and extracted with ethyl acetate (2×150 mL) and DCM (4×100 mL). The combined organic layers were concentrated and the residue was purified on a silica gel column to give 2.3 g (49%) of 4-(4-hydroxy-piperidin-1-ylmethyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde as a solid.

Workup

  1. concentrationThe reaction was concentrated to a volume of 30 mL
  2. extractionextracted with ethyl acetate (2×150 mL) and DCM (4×100 mL)
  3. concentrationThe combined organic layers were concentrated
  4. customthe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-83020fdb96f647c48f154eec790fc2a3
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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