Acetic Acid → 5-Chloro-6-(1-cyclobutyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid ethyl ester

HRID 493226Notes

Reaction equation

HRID 493226 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[C:14]([O:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[C:13]([Cl:23])=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5])[CH3:2].[C:24]1(=O)[CH2:27][CH2:26][CH2:25]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[C:14]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([CH:24]4[CH2:27][CH2:26][CH2:25]4)[CH2:19][CH2:18]3)[C:13]([Cl:23])=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 687264535-Chloro-3-methyl-6-(piperidin-4-yloxy)-benzofuran-2-carboxylic acid ethyl ester

Product 1

HCID 687261905-Chloro-6-(1-cyclobutyl-piperidin-4-yloxy)-3-methyl-benzofuran-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The above prepared 5-chloro-3-methyl-6-(piperidin-4-yloxy)-benzofuran-2-carboxylic acid ethyl ester (1.35 g, 3.32 mmol) was dissolved in 45 mL of CH2Cl2 and treated successively with cyclobutanone (0.506 g, 2 eq.), acetic acid (0.413 mL, 2 eq.) and sodium triacetoxyborohydride (1.529 g, 2 eq.), and the mixture then kept at ambient temperature for 5 h. Pouring onto crashed ice/NaHCO3, five fold extraction with AcOEt, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by followed by flash chromatography (SiO2, NEt3/AcOEt=2/98) generated 1.190 g of the title compound as white crystals.

Workup

  1. additionPouring
  2. extractionice/NaHCO3, five fold extraction with AcOEt
  3. washwashing with water and brine
  4. dry with materialdrying over magnesium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-59336076b7064d519935bb96322295df
Source dataset
uspto-grants-2009_05
Patent number
US07534788B2

Reaction notes

Loading…