Butyl bromide → 1,4-Dimethyl-6-pentyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

HRID 60391Notes

Reaction equation

HRID 60391 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[CH2:4][CH2:3]1.[Li][CH2:14][CH2:15][CH2:16][CH3:17].BrCCCC>C1COCC1>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([CH2:12][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:9][C:10]([CH3:11])=[C:5]2[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 8002Butyl bromideHCID 141770291,4,6-Trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 716778951,4-Dimethyl-6-pentyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 225 mg (1.39 mmol) of 1,4,6-trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine in 4 mL of THF was added 1.39 mL (2.22 mmol, 1.6 M in hexanes) of n-BuLi followed by 157 μL (1.46 mmol) of 1-bromobutane at −78° C. The reaction mixture was slowly warmed to room temperature and stirred for another 16 h. The reaction mixture was quenched by the addition of 10 mL of sat aq NH4Cl at 0° C. The mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (25 3.2 cm). Elution with 10:1 hexanes/ethyl acetate gave the product as a yellow oil: yield 0.20 g (66%); silica gel TLC Rf 0.15 (8:1:1 hexanes/ethyl acetate/MeOH); 1H NMR (CDCl3) δ 0.88 (t, 3H, J=7.2 Hz), 1.30-1.36 (m, 4H), 1.66 (quint, 2H, J=7.6 Hz), 2.08 (s, 3H), 2.55 (t, 2H, J=8.0 Hz), 2.81 (t, 2H, J=8.0 Hz), 2.88 (s, 3H), 3.38 (t, 2H, J=8.0 Hz) and 6.13 (s, 1H); 13C NMR (CDCl3) δ 14.1, 18.0, 22.6, 24.4, 29.6, 31.8, 33.3, 38.0, 52.5, 112.4, 118.2, 141.1, 159.1 and 163.7; mass spectrum, m/z 218.2 (M+) (theoretical 218.3); mass spectrum (APCI), m/z 219.1864 (M+H)+ (C14H23N2 requires 219.1861).

Workup

  1. customThe reaction mixture was quenched by the addition of 10 mL of sat aq NH4Cl at 0° C
  2. extractionThe mixture was extracted with EtOAc
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under diminished pressure
  6. customThe residue was purified by flash chromatography on a silica gel column (25 3.2 cm)
  7. washElution with 10:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-9b2cdc75c2a6419aa0ef4914963559e9
Source dataset
uspto-grants-2016_09
Patent number
US09440967B2

Reaction notes

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