Tetrahydrofuran → 1,4-Dimethyl-6-hexadecyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

HRID 60399

Reaction equation

HRID 60399 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].Br[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].[CH2:28]1COC[CH2:29]1>>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([CH2:12][CH2:17][CH2:16][CH2:15][CH2:14][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:28][CH3:29])=[CH:9][C:10]([CH3:11])=[C:5]2[CH2:4][CH2:3]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 127421-BromononaneHCID 141770291,4,6-Trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 716778991,4-Dimethyl-6-hexadecyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

Procedure

To a solution of 277 mg (1.71 mmol) of 1,4,6-trimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine in 5 mL of THF was added 1.71 mL (2.73 mmol, 1.6 M in hexanes) of n-BuLi followed by 518 μL (1.79 mmol) of 1-bromononane 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 white solid: yield 330 mg (52%); mp 43-45° C.; silica gel TLC Rf 0.25 (8:1:1 hexanes/ethyl acetate/MeOH); 1H NMR (CDCl3) δ 0.88 (t, 3H, J=7.2 Hz), 1.25-1.31 (m, 28H), 1.66 (quint, 2H, J=7.6 Hz), 2.08 (s, 3H), 2.55 (t, 2H, J=8.0 Hz), 2.80 (t, 2H, J=8.4 Hz), 2.90 (s, 3H), 3.38 (t, 2H, J=8.4 Hz) and 6.13 (s, 1H); 13C NMR (CDCl3) δ 14.1, 18.0, 22.7, 24.4, 29.38, 29.38, 29.57, 29.62, 29.65, 29.68, 29.72, 29.72, 29.72, 29.72, 29.72, 29.72, 30.0, 32.0, 33.2, 38.1, 52.4, 112.4, 118.2, 141.0, 159.1 and 163.7; mass spectrum, m/z 372.3 (M+) (theoretical 372.4); mass spectrum (APCI), m/z 373.3574 (M+H)+ (C25H45N2 requires 373.3583).

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-cc5177d09d07468481b96bcbbadf3d3c
Source dataset
uspto-grants-2016_09
Patent number
US09440967B2

Linked notes

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