Hydrochloric Acid → 4-(7-Bromo-5-methoxy-benzofuran-2-yl)-1-ethoxycarbonyl-piperidine

HRID 1938817Notes

Reaction equation

HRID 1938817 reaction equation
[Cl-].[Br:2][C:3]1[C:4]([O:31][C:32]([CH:34]2[CH2:39][CH2:38][N:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:36][CH2:35]2)=O)=[C:5]([CH2:11][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(=O)([O-])[O-].[K+].[K+].O.Cl>C(#N)C>[Br:2][C:3]1[C:4]2[O:31][C:32]([CH:34]3[CH2:35][CH2:36][N:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:38][CH2:39]3)=[CH:11][C:5]=2[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 11430Potassium CarbonateHCID 21470005(3-Bromo-2-((1-(ethoxycarbonyl)piperidine-4-carbonyl)oxy)-5-methoxybenzyl)triphenylphosphonium chloride

Product 1

HCID 111434314-(7-Bromo-5-methoxy-benzofuran-2-yl)-1-ethoxycarbonyl-piperidineYield 90%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In the course of 30 minutes, at 25° to 30°, with the exclusion of air, 50 g of [(3-bromo-2-[(1 -ethoxycarbonylpiperid4-yl)carbonyloxy]-5-methoxy-phenyl)methyl]-triphenyl-phosphonium chloride are introduced into a suspension of 20 g of ground potassium carbonate (anhydrous) in 100 ml of acetonitrile. The mixture is stirred for 2 hours at room temperature, then 80 ml of water are added thereto, and the mixture is acidified to pH 1.0 with concentrated hydrochloric acid. The organic phase is separated off and concentrated by evaporation. The oily residue is taken up in 50 ml of toluene and at 20°, in the course of 1 hour, 100 ml of hexane are added; the major portion (approx. 90%; content according to HPLC: 90%) of the triphenylphosphane oxide that forms crystallises out. The crystal suspension is filtered with suction and the filter cake is washed twice with 40 ml of hexane/toluene (3:2) each time. Concentration of the combined filtrates by evaporation and chromatography of the residue on silica gel with toluene/ethyl acetate (2:1) as eluant yield 4-(7-bromo-5-methoxy-benzofuran-2-yl)- 1-ethoxycarbonyl-piperidine [m.p.: 85°; 1H-NMR (360 MHz, CDCl3); 1.28 (t, 3H, CO2 CH2CH3), 1.69 (m, 2H), 2.09 (m, 2H), 2.95 (m, 3H), 3.80 (s, 3H, OCH3), 4.16 (q, 2H, CO2CH2CH3), 4.14 to 4.35 (br. m, 2H), 6.36 (s, 1H), 6.90 (d, 1H), 7.00 (d, 1H) ppm]; yield 90% of the theoretical yield.

Workup

  1. customThe organic phase is separated off
  2. concentrationconcentrated by evaporation
  3. customis taken up in 50 ml of toluene and at 20°, in the course of 1 hour, 100 ml of hexane
  4. additionare added
  5. customthe major portion (approx. 90%; content according to HPLC: 90%) of the triphenylphosphane oxide that forms crystallises out
  6. filtrationThe crystal suspension is filtered with suction
  7. washthe filter cake is washed twice with 40 ml of hexane/toluene (3:2) each time
  8. customConcentration of the combined filtrates by evaporation and chromatography of the residue on silica gel with toluene/ethyl acetate (2:1) as eluant

Sources & evidence

ORD record
ord-94c9cda50745423eb16d419044c0b2a6
Source dataset
uspto-grants-1997_12
Patent number
US05693807

Reaction notes

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