1-[2-(4-Bromophenoxy)ethyl]piperidine → 6-Methoxy-2-(4-Methoxyphenyl)-3-[4-[2-(1-Piperidinyl)ethoxy]phenyl]benzo[b]thiophene-3-Methanimine

HRID 850730Notes

Reaction equation

HRID 850730 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])(CC)C.[CH3:22][O:23][C:24]1[CH:25]=[CH:26][C:27]2[C:31]([C:32]#[N:33])=[C:30]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[S:29][C:28]=2[CH:42]=1>O1CCCC1>[CH3:22][O:23][C:24]1[CH:25]=[CH:26][C:27]2[C:31]([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][N:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)([CH:32]=[NH:33])[CH:30]([C:34]3[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=3)[S:29][C:28]=2[CH:42]=1

Participants

5

Reactant 3

HCID 8671951-[2-(4-Bromophenoxy)ethyl]piperidineHCID 154582706-Methoxy-2-(4-methoxyphenyl)-1-benzothiophene-3-carbonitrileHCID 178418400CID 53628100

Product 1

HCID 193650696-Methoxy-2-(4-Methoxyphenyl)-3-[4-[2-(1-Piperidinyl)ethoxy]phenyl]benzo[b]thiophene-3-Methanimine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 4-[2-(1-piperidinyl)ethoxy]bromobenzene (114.5 mg, 0.357 mmol) in tetrahydrofuran (2 ml) at -78° C. is added secbutyl lithium (0.275 ml of a 1.3 M solution, 0.358 mmol). The resulting solution is stirred at that temperature for 30 minutes, then a solution of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene-3-carbonitrile (98.5 mg, 0.333 mmol) in tetrahydrofuran (1 ml) is added. The resulting mixture is stirred and allowed to warm to room temperature overnight. The reaction is then quenched by addition of saturated aqueous ammonium chloride (2 ml) and partitioned between methylene chloride and water. The layers are separated, and the aqueous layer extracted again with methylene chloride. The organic layers are combined, dried over magnesium sulfate, filtered and concentrated to an oil, which is chromatographed on silica gel (95:5:0.2 dichloromethane:methanol:triethylamine) to afford a fraction containing desired product. This fraction is concentrated and further chromatographed on silica gel (10:5:1 hexanes:dichloromethane:triethylamine) to afford, after drying in vacuo, 78.6 mg (47%) of title compound as an oil. IR (KBr) 2933, 1607, 1501, 1249, 1032 cm-1 ; 1H NMR (CDCl3): δ7.71 (d, 2 H, J=8.4 Hz), 7.42 (d, 2 H, J=8.7 Hz), 7.26 (m, 2 H), 6.90 (dd, 1 H, J=8.9, 2.2 Hz), 6.80 (m, 4 H), 4.10 (t, 2 H, J=6.0 Hz), 3.87 (s, 3 H), 3.76 (s, 3 H), 22.76 (t, 2 H, J=6.0 Hz), 2.50 (m, 4 H), 1.58 (m, 4 H), 1.44 (m, 2 H); 13C NMR (CDCl3): d 173.4, 161.4, 159.6, 157.7, 139.9, 138.5, 134.0, 131.1, 130.5, 129.9, 129.7, 125.9, 123.8, 114.7, 114.5, 114.2, 104.8, 66.2, 57.9, 55.7, 55.3, 55.1, 26.0, 24.3. Anal. Calcd. for C30H32N2O3S: C, 71.97; H, 6.44; N, 5.60; S, 6.40. Found: C, 71.73; H, 6.36; N, 5.41; S, 6.27.

Workup

  1. stirringThe resulting mixture is stirred
  2. customThe reaction is then quenched by addition of saturated aqueous ammonium chloride (2 ml)
  3. custompartitioned between methylene chloride and water
  4. customThe layers are separated
  5. extractionthe aqueous layer extracted again with methylene chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to an oil, which
  9. customis chromatographed on silica gel (95:5:0.2 dichloromethane:methanol:triethylamine)
  10. customto afford a fraction

Sources & evidence

ORD record
ord-974401e24fb14ca6a43641b3f7d31821
Source dataset
uspto-grants-2000_01
Patent number
US06018056

Reaction notes

Loading…