1-Bromoheptane → 1,4-dimethyl-6-octyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

HRID 60405

Reaction equation

HRID 60405 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]CCCC.Br[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]>C1COCC1>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([CH2:12][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:9][C:10]([CH3:11])=[C:5]2[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 123691-BromoheptaneHCID 141770291,4,6-Trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 716787341,4-dimethyl-6-octyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution containing −490 mg (2.71 mmol) of 1,4,6-Trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine in 7.2 mL of THF was added 2.70 mL (4.34 mmol) of n-BuLi (1.6 M in hexanes) followed by 4504 (509 mg, 2.85 mmol) of 1-bromoheptane at −78° C. The reaction mixture was slowly warmed to room temperature and stirred for 16 h. The reaction mixture was quenched by the addition of 25 mL of sat aq. NH4Cl at 0° C. The mixture was extracted with three 40-mL portions, of EtOAc. The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under diminished pressure. The residue was purified via flash chromatography on a silica gel column (42×2.5 cm). Step gradient elution with 1:10→1:4 ethyl acetate-hexanes as eluent gave 1,4-dimethyl-6-octyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine as a yellow oil: yield 402 mg (57%); silica gel TLC Rf 0.36 (8:1:1 hexanes-ethyl acetate-methanol); 1H NMR (CDCl3) δ 0.79 (t, 2H, J=7.2 Hz), 1.16-1.30 (m, 10H), 1.58 (quint, 2H, J=8.0 Hz), 2.00 (s, 3H), 2.48 (t, 2H, J=8.0 Hz), 2.72 (t, 2H, J=8.4 Hz), 2.82 (s, 3H), 3.38 (t, 2H, J=8.4 Hz), 6.14 (s, 1H).

Workup

  1. customThe reaction mixture was quenched by the addition of 25 mL of sat aq. NH4Cl at 0° C
  2. extractionThe mixture was extracted with three 40-mL portions, of EtOAc
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under diminished pressure
  7. customThe residue was purified via flash chromatography on a silica gel column (42×2.5 cm)
  8. washStep gradient elution with 1:10→1:4 ethyl acetate-hexanes as eluent

Sources & evidence

ORD record
ord-227f477518794804ad7242f9edc3b609
Source dataset
uspto-grants-2016_09
Patent number
US09440967B2

Linked notes

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