Phenethyl bromide → 2-(Diethoxy-phosphoryl)-4-phenyl-butyric acid tert-butyl ester

HRID 902937Notes

Reaction equation

HRID 902937 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]([O-:12])=[O:11])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[H-].[Na+].[CH2:15](Br)[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[C:17]([O:11][C:10](=[O:12])[CH:9]([P:4]([O:3][CH2:1][CH3:2])([O:6][CH2:7][CH3:8])=[O:5])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:22])([CH3:18])[CH3:16]

Participants

5

Reactant 3

HCID 7666Phenethyl bromideHCID 24758Sodium hydrideHCID 6992230Diethylphosphonoacetate

Product 1

HCID 865943852-(Diethoxy-phosphoryl)-4-phenyl-butyric acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Diethylphosphonoacetate (1.00 g, 3.96 mmol) was added drop wise at 0° C. to a stirring suspension of sodium hydride (0.095 g, 3.96 mmol) in anhydrous THF (50 mL). The mixture was then allowed to stir for 10 minutes at 0° C. and then for 1 hour at room temperature before it was cooled again to 0° C. followed by the addition of phenethyl bromide (0.73 g, 3.96 mmol). The mixture was then allowed to proceed for 24 hours at room temperature. The solvent was evaporated and the residue was taken-up in water and extracted 4 times with ethyl acetate. The organic extracts were combined, washed with water and brine, dried using magnesium sulfate, filtered and evaporated. The crude residue was purified by flash chromatography (ethyl acetate in hexanes, 10%-50%) to afford the desired compound as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.18 (m, 2H), 7.09 (m, 2H), 4.07-3.99 (m, 4H), 2.82-2.72 (m, 1H), 2.69-2.60 (m, 1H), 2.54-2.45 (m, 1H), 2.25-2.12 (m, 1H), 2.08-1.94 (m, 1H), 1.41 (s, 9H), 1.24-1.18 (m, 6H); 13C (CDCl3, 400 MHz) δ 167.7, 140.4, 128.3, 128.2, 125.9, 81.5, 62.2, 46.3, 45.0, 34.1, 28.5, 27.7, 16.1; 31P (CDCl3, 400 MHz) δ 23.7. HRMS calcd. for C18H29O5P 356.1753, found 356.1757.

Workup

  1. temperaturefor 1 hour at room temperature before it was cooled again to 0° C.
  2. waitto proceed for 24 hours at room temperature
  3. customThe solvent was evaporated
  4. extractionextracted 4 times with ethyl acetate
  5. washwashed with water and brine
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude residue was purified by flash chromatography (ethyl acetate in hexanes, 10%-50%)

Sources & evidence

ORD record
ord-9bb4ffc46c2a464bbc91c0a6215a2010
Source dataset
uspto-grants-2008_04
Patent number
US07365091B2

Reaction notes

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