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 1811342Notes

Reaction equation

HRID 1811342 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-trifloromethyl-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-d66a4125e10047628aff0268458042a9
Source dataset
uspto-grants-2013_01
Patent number
US08362251B2

Reaction notes

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