N-(4-Bromobutyl)phthalimide → 1-[2-[4-[[2-[4-(4-Aminobutoxy)phenyl]-benzo[b]thiophen-3-yl]methyl]phenoxy]ethyl]-pyrrolidine

HRID 1070355Notes

Reaction equation

HRID 1070355 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[C:9]=2[CH2:17][C:18]2[CH:31]=[CH:30][C:21]([O:22][CH2:23][CH2:24][N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:43][CH2:44][CH2:45][CH2:46][N:47]1C(=O)C2=CC=CC=C2C1=O>C1COCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[NH2:47][CH2:46][CH2:45][CH2:44][CH2:43][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[C:9]=2[CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:22][CH2:23][CH2:24][N:25]3[CH2:26][CH2:27][CH2:28][CH2:29]3)=[CH:30][CH:31]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 93575N-(4-Bromobutyl)phthalimideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 224626554-[3-[4-[2-(1-Pyrrolidinyl)ethoxy]benzyl]benzo[b]thiophen-2-yl]phenol

Product 1

HCID 217050981-[2-[4-[[2-[4-(4-Aminobutoxy)phenyl]-benzo[b]thiophen-3-yl]methyl]phenoxy]ethyl]-pyrrolidineYield 87.7%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-[2-[4-[[2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]methyl]phenoxy]ethyl]pyrrolidine (53 mg, 0.123 mmol) in THF (1 mL) was added a solution of potassium bis(trimethylsilyl)amide (0.271 mL of 0.5 M, 1.36 mmol, 1.1 eq.) in toluene at ambient temperature. After 80 min, N-(4-bromobutyl)phthalimide (75 mg, 0.265 mmol, 2.2 eq) was added and the reaction heated at reflux for 18 h. The reaction was cooled to ambient temperature, diluted with ethyl acetate (50 mL) then washed with 10% aqueous sodium bicarbonate (20 mL). The solvent was removed under reduced pressure then the residue purified by flash chromatography (20:1 CHCl3: MeOH then 5:1 CHCl3: MeOH) to give the protected amine as a tan solid (54 mg, 70%) and recovered starting material (8 mg).

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 18 h
  3. washthen washed with 10% aqueous sodium bicarbonate (20 mL)
  4. customThe solvent was removed under reduced pressure
  5. customthe residue purified by flash chromatography (20:1 CHCl3

Sources & evidence

ORD record
ord-3562726c553245b686a7bd94622b8fa4
Source dataset
uspto-grants-2001_06
Patent number
US06251921B1

Reaction notes

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