Ethyl Acetate → {2-[4-(6-Methoxy-3-methyl-2-phenyl-naphthalen-1-yloxy)-phenyl]-vinyl}-phosphonic acid diethyl ester

HRID 1992960Notes

Reaction equation

HRID 1992960 reaction equation
[CH2:1]([P:10](=[O:17])([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13])P(=O)(OCC)OCC.[Li]CCCC.[CH3:23][C:24]1[C:25]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[C:26]([O:36][C:37]2[CH:44]=[CH:43][C:40]([CH:41]=O)=[CH:39][CH:38]=2)[C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([O:34][CH3:35])=[CH:29][CH:28]=2.CCOC(C)=O>C1COCC1.O>[CH2:15]([O:14][P:10]([CH:1]=[CH:41][C:40]1[CH:39]=[CH:38][C:37]([O:36][C:26]2[C:27]3[C:32](=[CH:31][C:30]([O:34][CH3:35])=[CH:29][CH:28]=3)[CH:33]=[C:24]([CH3:23])[C:25]=2[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:44][CH:43]=1)(=[O:17])[O:11][CH2:12][CH3:13])[CH3:16]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 15455Tetraethyl methylenediphosphonateHCID 860871594-[(6-Methoxy-3-methyl-2-phenyl-1-naphthyl)oxy]benzaldehydeHCID 178418339Butyllithium

Product 1

HCID 86616666{2-[4-(6-Methoxy-3-methyl-2-phenyl-naphthalen-1-yloxy)-phenyl]-vinyl}-phosphonic acid diethyl esterYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of tetraethyl methylenediphosphonate (0.11 mL, 0.537 mmol) in hexanes (1 mL) was slowly added 1.6 M nBuLi (0.051 mL, 0.537 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 h under nitrogen. The reaction mixture was cooled to 0° C. then a solution of 4-[(6-methoxy-3-methyl-2-phenyl-1-naphthyl)oxy]benzaldehyde (8) (0.198 g, 0.537 mmol) in THF (1 mL) was added dropwise. After addition, reaction mixture was stirred at above temperature for 10 min then heated at 80° C. for 3 h. Reaction mixture was cooled to room temperature then diluted with water followed by EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with water followed by brine, dried over MgSO4, filtered and concentrated to give oil. The crude oil was chromatographed with 9% EtOAc in hexanes followed by straight MeOH to give 0.151 g (56%) of the title compound (197) as oil. 1H NMR (400 MHz, d-CDCl3): δ 1.33 (t, J=7.1 Hz, 6H), 2.25 (s, 3H), 3.93 (s, 3H), 4.07-4.11 (m, 4H), 6.01 (t, J=17.6 Hz, 1H), 6.59 (d, J=8.8 Hz, 2H), 7.03 (dd, J1=2.4, J2=9.2 Hz, 1H), 7.12-7.14 (m, 3H), 7.22-7.28 (m, 5H), 7.30-7.36 (m, 1H), 7.40 (s, 1H), 7.69 (d, J=9.1 Hz, 1H).

Workup

  1. customat 0° C
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. additionAfter addition, reaction mixture
  4. stirringwas stirred at above temperature for 10 min
  5. temperaturethen heated at 80° C. for 3 h
  6. customReaction mixture
  7. temperaturewas cooled to room temperature
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with EtOAc
  10. washThe combined organic layers were washed with water
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give oil
  15. customThe crude oil was chromatographed with 9% EtOAc in hexanes

Sources & evidence

ORD record
ord-dd6dec4daf40470788737e118a3cf5b6
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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