2-Iodoxybenzoic acid → 5-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde

HRID 905883Notes

Reaction equation

HRID 905883 reaction equation
[CH2:1]([N:3]([CH2:22][CH3:23])[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][C:9]2[NH:12][C:13]([CH2:19][OH:20])=[C:14]([C:15]([F:18])([F:17])[F:16])[C:8]=2[C:7]1=[O:21])[CH3:2].O.CC1C=CC(S(O)(=O)=O)=CC=1.I(C1C=CC=CC=1C(O)=O)(=O)=O>>[CH2:22]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][C:9]2[NH:12][C:13]([CH:19]=[O:20])=[C:14]([C:15]([F:16])([F:18])[F:17])[C:8]=2[C:7]1=[O:21])[CH3:23]

Participants

4

Reactant 3

HCID 1087942-Iodoxybenzoic acidHCID 521998p-Toluenesulfonic acid monohydrateHCID 666073725-(2-Diethylamino-ethyl)-2-hydroxymethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one

Product 1

HCID 866376915-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehydeYield 33.8%

Procedure

A stirred solution of 5-(2-diethylamino-ethyl)-2-hydroxymethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (1.208 g, 3.63 mmol) and 4-methylbenzenesulfonic acid monohydrate (690 mg, 3.63 mmol) in 8 ml of N,N-dimethyl sulfoxide was added dropwise with 2-iodoxybenzoic acid (1.63 g, 5.8 mmol) in 8 ml of N,N-dimethyl sulfoxide. Upon the completion of the addition, the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was added with ice to quench the reaction and filtered. The filtrate was added with saturated sodium carbonate to adjust pH9˜10, extracted with dichloromethane (50 ml×5). The combined organic phase was washed with saturated sodium carbonate (10 ml), saturated sodium chloride (10 ml), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by the silica gel column chromatography with dichloromethane:n-hexane:methanol:ammonia (200:20:10:0.5) as eluents to give 5-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde (407 mg, 28%) as a yellow solid.

Workup

  1. additionUpon the completion of the addition
  2. additionThe reaction mixture was added with ice
  3. customto quench
  4. customthe reaction
  5. filtrationfiltered
  6. additionThe filtrate was added with saturated sodium carbonate
  7. extractionextracted with dichloromethane (50 ml×5)
  8. washThe combined organic phase was washed with saturated sodium carbonate (10 ml), saturated sodium chloride (10 ml)
  9. dry with materialdried with anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by the silica gel column chromatography with dichloromethane:n-hexane:methanol:ammonia (200:20:10:0.5) as eluents

Sources & evidence

ORD record
ord-192b7ccc58444904a28d3844a5b5f5da
Source dataset
uspto-grants-2011_09
Patent number
US08012966B2

Reaction notes

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