Acetic Acid → 3-Methyl-4-(1-pyridin-3-ylmethyl-piperidin-3-ylmethoxy)-benzofuran-2-carboxylic acid ethyl ester

HRID 843170Notes

Reaction equation

HRID 843170 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][CH:18]3[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]3)[C:9]=2[C:10]=1[CH3:11])=[O:5])[CH3:2].[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]=O)[CH:25]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][CH:18]3[CH2:23][CH2:22][CH2:21][N:20]([CH2:30][C:26]4[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=4)[CH2:19]3)[C:9]=2[C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 103713-PyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 538037073-Methyl-4-(piperidin-3-ylmethoxy)-benzofuran-2-carboxylic acid ethyl ester

Product 1

HCID 544265053-Methyl-4-(1-pyridin-3-ylmethyl-piperidin-3-ylmethoxy)-benzofuran-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Methyl-4-(piperidin-3-ylmethoxy)-benzofuran-2-carboxylic acid ethyl ester (700 mg), pyridine-3-aldehyde (700 μl) and acetic acid (1 ml) were dissolved in THF (20 ml). The solution was stirred at room temperature for four hours. To the solution was added NaB(OAc)3H (1.4 g) and the resulting suspension was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium hydrogencarbonate solution and brine. The organic solvent was dried over anhydrous sodium sulfate and evaporated to dryness. The residue was purified by silica gel column chromatography developed by dichloromethane-methanol to give 3-methyl-4-(1-pyridin-3-ylmethyl-piperidin-3-ylmethoxy)-benzofuran-2-carboxylic acid ethyl ester (777 mg) as a colorless oil. FAB-MS: m/z 409 (MH+); 1H-NMR (CDCl3): δ 1.15-2.30 (7H, m), 1.44 (3H, t, J=7 Hz), 2.58 (3H, s), 2.80 (1H, br d, J=11 Hz), 2.96 (1H, br d, J=8 Hz), 3.48 (1H, d, J=13.5 Hz), 3.57 (1H, d, J=13.5 Hz), 3.89 (1H, dd, J1=9 Hz, J2=8 Hz), 3.96 (1H, dd, J1=9 Hz, J2=5 Hz), 4.43 (2H, q, J=7 Hz), 6.57 (1H, d, J=8 Hz), 7.10 (1H, d, J=8 Hz), 7.21 (1H, dd, J1=8 Hz, J2=5 Hz), 7.28 (1H, t, J=8 Hz), 7.67 (1H, br d, J=8 Hz), 8.49 (1H, dd, J1=5 Hz, J2=1.5 Hz), 8.54 (1H, d, J=1.5 Hz).

Workup

  1. stirringthe resulting suspension was stirred overnight at room temperature
  2. washwashed with saturated sodium hydrogencarbonate solution and brine
  3. dry with materialThe organic solvent was dried over anhydrous sodium sulfate
  4. customevaporated to dryness
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-73184b4f2c4c4b628759faf27caf0b8d
Source dataset
uspto-grants-2002_04
Patent number
US06376491B1

Reaction notes

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