Sodium hydride → 3-{4-[2-(Tert-butoxycarbonyl-heptyl-amino)-ethyl]-phenyl}-2-ethoxy-acrylic acid ethyl ester

HRID 47791Notes

Reaction equation

HRID 47791 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:25])[CH:7](P(C1C=CC=CC=1)(C1C=CC=CC=1)=O)[O:8][CH2:9][CH3:10])[CH3:4].[C:26]([O:30][C:31](=[O:50])[N:32]([CH2:40][CH2:41][C:42]1[CH:47]=[CH:46][C:45]([CH:48]=O)=[CH:44][CH:43]=1)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[CH2:3]([O:5][C:6](=[O:25])[C:7]([O:8][CH2:9][CH3:10])=[CH:48][C:45]1[CH:46]=[CH:47][C:42]([CH2:41][CH2:40][N:32]([C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:50])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])=[CH:43][CH:44]=1)[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 574383762-Diphenylphosphinoyl-2-ethoxyacetic acid ethyl esterHCID 86586368[2-(4-Formyl-phenyl)-ethyl]-heptyl-carbamic acid tert-butyl ester

Product 1

HCID 698846713-{4-[2-(Tert-butoxycarbonyl-heptyl-amino)-ethyl]-phenyl}-2-ethoxy-acrylic acid ethyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of 60% by weight sodium hydride oil dispersion (6.97 mmol, 277 mg) in anhydrous tetrahydrofuran (20 mL) cooled to 0° C. was added 2-diphenylphosphinoyl-2-ethoxyacetic acid ethyl ester (3.80 mmol, 1.26 g) followed by [2-(4-formyl-phenyl)-ethyl]-heptyl-carbamic acid tert-butyl ester (3.46 mmol, 1.2 g) dissolved in anhydrous tetrahydrofuran (15 mL). The resulting heterogeneous solution was heated to reflux for one hour. The mixture was cooled to room temperature, quenched by the addition of ethanol (2 mL) and diluted with water (20 mL). The aqueous layer was isolated and extracted with diethyl ether (3×). The organic layers were combined, washed with saturated NaHCO3 (2×), brine (1×), dried over anhydrous sodium sulfate, and concentrated to a crude yellow oil. The crude oil was chromatographed on silica gel (20% ethyl acetate/hexanes) to give 3-{4-[2-(tert-butoxycarbonyl-heptyl-amino)-ethyl]-phenyl}-2-ethoxy-acrylic acid ethyl ester as a clear oil (700 mg, 44%).

Workup

  1. temperatureThe resulting heterogeneous solution was heated
  2. temperatureto reflux for one hour
  3. temperatureThe mixture was cooled to room temperature
  4. customquenched by the addition of ethanol (2 mL)
  5. additiondiluted with water (20 mL)
  6. customThe aqueous layer was isolated
  7. extractionextracted with diethyl ether (3×)
  8. washwashed with saturated NaHCO3 (2×), brine (1×)
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated to a crude yellow oil
  11. customThe crude oil was chromatographed on silica gel (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-83ad992653574de698a11b0c55e23db4
Source dataset
uspto-grants-2004_03
Patent number
US06699904B2

Reaction notes

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