Pyridine → (3-Bromo-2-((1-(ethoxycarbonyl)piperidine-4-carbonyl)oxy)-5-methoxybenzyl)triphenylphosphonium chloride

HRID 486285Notes

Reaction equation

HRID 486285 reaction equation
[Cl:1][C:2]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5]1)=[O:3].[Cl-].[Br:16][C:17]1[C:18]([OH:45])=[C:19]([CH2:25][P+:26]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:20]=[C:21]([O:23][CH3:24])[CH:22]=1.N1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[Cl-:1].[Br:16][C:17]1[C:18]([O:45][C:2]([CH:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5]2)=[O:3])=[C:19]([CH2:25][P+:26]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:20]=[C:21]([O:23][CH3:24])[CH:22]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 10340Sodium CarbonateHCID 10929346(3-Bromo-2-hydroxy-5-methoxybenzyl)triphenylphosphonium chlorideHCID 11096122Ethyl 4-(chlorocarbonyl)-1-piperidinecarboxylate

Product 1

HCID 21470005(3-Bromo-2-((1-(ethoxycarbonyl)piperidine-4-carbonyl)oxy)-5-methoxybenzyl)triphenylphosphonium chlorideYield 66%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

With the exclusion of air, 43.9 g of 4-chlorocarbonyl-1-ethoxycarbonyl-piperidine are dissolved in 250 ml of anhydrous acetonitrile (degassed) and 53.4 g of [(3-bromo-2-hydroxy-5-methoxy-phenyl)methyl]-triphenyl-phosphonium chloride are added to the solution. In the course of 30 minutes, at 25° to 30°, 20 g of pyridine are added dropwise to the resulting suspension. The mixture is heated for 5 hours under reflux and is then hydrolysed with 100 ml of sodium carbonate solution (15%); the organic phase is separated off, washed in succession with 100 ml of 1N hydrochloric acid and 100 ml of water and concentrated by evaporation in vacuo and the oily residue that remains is dissolved in 50 ml of dichloromethane. In the course of 30 minutes, at 20°, with vigorous stirring, 200 ml of ethyl acetate are added dropwise to that solution and the product crystallises out. The resulting crystal suspension is concentrated to 150 ml under a weak vacuum using a rotary evaporator and then stirred for 2 hours at 0°. Filtering with suction and drying yield [(3-bromo-2-[(1-ethoxycarbonylpiperid-4-yl)carbonyloxy]-5-methoxy-phenyl)methyl]-triphenyl-phosphonium chloride [m.p.: 196°, IR (KBr): 3415, 3060, 2855, 2780, 1600, 1565, 1385, 1270, 1190, 1165 cm-1 ; 1H-NMR (360 MHz, CDCl3): 1.28 (t, 3H, CO2CH2CH3), 1.45 (m, 2H), 1.75 (m, 2H), 2.58 (m, 1H), 2.87 (m, 2H), 3.47 (s, 3H, OCH3), 4.00 (m, 2H), 4.13 (q, 2H, CO2CH2CH3), 5.37 (br. d, 2H, CH2P+), 6.87 (dd, 1H), 7.07 (dd, 1H), 7.54 to 7.87 (m, 15H) ppm]; yield 66% of the theoretical yield.

Workup

  1. temperatureThe mixture is heated for 5 hours
  2. temperatureunder reflux
  3. customthe organic phase is separated off
  4. washwashed in succession with 100 ml of 1N hydrochloric acid and 100 ml of water
  5. concentrationconcentrated by evaporation in vacuo
  6. dissolutionthe oily residue that remains is dissolved in 50 ml of dichloromethane
  7. additionIn the course of 30 minutes, at 20°, with vigorous stirring, 200 ml of ethyl acetate are added dropwise to that solution
  8. customthe product crystallises out
  9. concentrationThe resulting crystal suspension is concentrated to 150 ml under a weak vacuum
  10. customa rotary evaporator
  11. filtrationFiltering with suction
  12. customdrying

Sources & evidence

ORD record
ord-48b2aee68972423b8f5fd9a3a89b2bb0
Source dataset
uspto-grants-1994_03
Patent number
US05290939

Reaction notes

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