Formaldehyde → 3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1-Pentyl-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one

HRID 1715213Notes

Reaction equation

HRID 1715213 reaction equation
[OH:1][C:2]1[C:3]([CH:11]2[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[N:13]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:12]2=[O:25])=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.C([N-]C(C)C)(C)C.[Li+].[CH2:34]=[O:35]>O1CCCC1>[OH:1][C:2]1[C:3]([C:11]2([CH2:34][OH:35])[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[N:13]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:12]2=[O:25])=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2724682Lithium diisopropylamideHCID 119627753-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one

Product 1

HCID 119628133-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1-Pentyl-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-oneYield 112%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one (1.60 g, 4.70 mmol) in anhydrous tetrahydrofuran (30.0 mL) was added a solution of pre-prepared lithium diisopropylamide (10.3 mmol) in anhydrous tetrahydrofuran (30.0 mL) at −78° C. The reaction mixture was stirred at −78° C. for 0.5 h followed by the addiotion of para-formaldehyde (0.85 g, 28.2 mmol) in one portion. The reaction was stirred at −78° C. for 2 h and quenched with saturated ammonium chloride (20.0 mL). After the organic solvent was removed under reduced pressure, the residue was diluted with ethyl acetate (50.0 mL). The organic layer was washed with brine (30.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness to give the title compound (1.95 g, 100%): 1H NMR (300 MHz, CDCl3) δ 8.22 (dd, 1H), 7.22-7.12 (m, 2H), 6.51 (s, 1H), 6.06 (s, 1H), 5.83 (d, 2H), 4.89 (s, 2H), 3.83-3.61 (m, 2H), 1.75-1.61 (m, 2H), 1.39-1.29 (m, 4H), 0.89 (t, 3H).

Workup

  1. stirringThe reaction was stirred at −78° C. for 2 h
  2. customquenched with saturated ammonium chloride (20.0 mL)
  3. customAfter the organic solvent was removed under reduced pressure
  4. additionthe residue was diluted with ethyl acetate (50.0 mL)
  5. washThe organic layer was washed with brine (30.0 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-0bbc4b6c72854f979fbe14d484f33a87
Source dataset
uspto-grants-2010_09
Patent number
US07799798B2

Reaction notes

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