Hexane → HCID 10308542, compound

HRID 1986808Notes

Reaction equation

HRID 1986808 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3]C.CCCCCC.[NH:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][CH2:13]1.ClCCCI.C([O-])([O-])=O.[K+].[K+].[CH2:33]([CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)[CH2:34][CH2:35][CH3:36]>O1CCCC1.O>[CH2:33]([CH:37]1[CH2:42][CH2:41][N:40]([CH2:1][CH2:2][CH2:3][N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH2:39][CH2:38]1)[CH2:34][CH2:35][CH3:36]

Participants

9

Reactant 6

HCID 8058HexaneHCID 11430Potassium CarbonateHCID 694601,2,3,4-TetrahydroquinolineHCID 813631-Chloro-3-iodopropaneHCID 132838674-ButylpiperidineHCID 178418339Butyllithium

Product 1

HCID 10308542HCID 10308542, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of n-butyllithium in hexane (1.5M, 7.3 mL, 11 mmol) was added drop wise to a solution of 1,2,3,4-tetrahydro-quinoline (1.256 mL, 10 mmol) in tetrahydrofuran (10 mL) at −78° C. under an atmosphere of argon. The reaction mixture was stirred for ½ h then 1-chloro-3-iodopropane (1.0 mL, 9.5 mmol) was added. The reaction mixture was stirred at −78° C. for ½ h then stirred for additional 16 h at room temperature. Tetrahydrofuran was evaporated off and the solid was dissolved in acetonitrile (10 mL). KI (1.83 g, 11 mmol), K2CO3 (2.76 g, 20 mmol) and 4-butylpiperidine (1.66 mL, 10 mmol) were added. The slurry was stirred at 50° C. for 48 h then water (10 mL) was added and the product was extracted with ethyl acetate (2×20 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The product was purified by column chromatography (eluent: ethyl acetate) to give the title compound (1.11 g, 35%) Oxalate-salt was prepared from oxalic acid (1.1 eq.) in acetone. HPLC-MS: M+1+=315.1 (MS (%)=95). 1H NMR (400 MHz, CDCl3): δ=0.89 (3H, t), 1.18-1.34 (9H, m), 1.64-1.70 (2H, m), 1.79 (2H, quin.), 1.85-1.98 (4H, m), 2.36 (2H, t), 2.74 (2H, t), 2.92 (2H, broad d), 3.24-3.31 (4H, m), 6.54 (1H, ddd), 6.60 (1H, dd), 6.93 (1H, dd), 7.03 (1H, ddd). 13C NMR (CDCl3): d 14.3, 22.5, 23.1, 24.2, 28.4, 29.3, 32.7, 36.0, 36.5, 49.6, 49.8, 54.4, 56.7, 110.9, 115.5, 122.5, 127.3, 129.3, 145.6.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for ½ h
  2. stirringthen stirred for additional 16 h at room temperature
  3. customTetrahydrofuran was evaporated off
  4. dissolutionthe solid was dissolved in acetonitrile (10 mL)
  5. stirringThe slurry was stirred at 50° C. for 48 h
  6. extractionthe product was extracted with ethyl acetate (2×20 mL)
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe product was purified by column chromatography (eluent: ethyl acetate)

Sources & evidence

ORD record
ord-6279e2670df34445ba52056972bd4a8c
Source dataset
uspto-grants-2009_06
Patent number
US07550459B2

Reaction notes

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