Triethylamine → HCID 17964302, compound

HRID 457800Notes

Reaction equation

HRID 457800 reaction equation
C[O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10]Br)[CH:5]=1.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]([CH2:28][C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[CH:20]=2)[CH2:15][CH2:14]1.C(N(CC)CC)C>ClCCl>[N:31]1[CH:32]=[CH:33][CH:34]=[C:29]([CH2:28][N:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:19]([CH:16]3[CH2:17][CH2:18][N:13]([CH2:10][C:6]4[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=4)[C:3]([OH:2])=[O:12])[CH2:14][CH2:15]3)=[CH:20]2)[CH:30]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 517981Methyl 3-(bromomethyl)benzoateHCID 17964317HCID 17964317, compound

Product 1

HCID 17964302HCID 17964302, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution containing 1.2 g (52 mmol) of 3-bromomethyl-benzoic acid methyl ester in 10 mL of anhydrous dichloromethane was added dropwise over a solution of 1.5 g (5 mmol) 3-piperidin-4-yl-1-pyridin-3-ylmethyl-1H-indole and 0.8 mL (55 mmol) of triethylamine in 35 of anhydrous dichloromethane. After stirring at room temperature for 5 hours, the crude mixture was washed with water, saturated solution of sodium hydrogencarbonate and water. The organic phase was dried and the solvent was removed under reduced pressure. The crude mixture was purified by flash chromatography over silica gel affording 0.95 g (43% of yield) of 3-[4-(1-pyridin-3-ylmethyl-1H-indol-3-yl)-piperidin-1-ylmethyl]-benzoic acid methyl ester. This ester was dissolved in 15 mL of methanol and hydrolised with NaOH 1N at room temperature for 12 hours. The crude mixture was neutralised with HCl 1N and then the solvent was removed under reduced pressure. The solid residue was washed with water and dichloromethane and the corresponding acid (0.6 g, 77% of yield) was isolated by filtration.

Workup

  1. washthe crude mixture was washed with water, saturated solution of sodium hydrogencarbonate and water
  2. customThe organic phase was dried
  3. customthe solvent was removed under reduced pressure
  4. customThe crude mixture was purified by flash chromatography over silica gel affording 0.95 g (43% of yield) of 3-[4-(1-pyridin-3-ylmethyl-1H-indol-3-yl)-piperidin-1-ylmethyl]-benzoic acid methyl ester
  5. dissolutionThis ester was dissolved in 15 mL of methanol and hydrolised with NaOH 1N at room temperature for 12 hours
  6. customthe solvent was removed under reduced pressure
  7. washThe solid residue was washed with water and dichloromethane
  8. customthe corresponding acid (0.6 g, 77% of yield)
  9. customwas isolated by filtration

Sources & evidence

ORD record
ord-cce0396ce1a146afa6fe390317c49fa7
Source dataset
uspto-grants-2007_03
Patent number
US07189741B2

Reaction notes

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