Water → HCID 70202154, compound

HRID 1464136Notes

Reaction equation

HRID 1464136 reaction equation
[CH3:1][CH:2]([CH3:17])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH:12]=O)=[C:6]([C:14]([OH:16])=[O:15])[CH:5]=1.C(OCC)(=O)C[C:20]([O:22]CC)=[O:21].N1[CH:34]=[CH:33][CH:32]=[CH:31]C=1.[OH2:35].C1C[O:39][CH2:38][CH2:37]1>C(Cl)(Cl)(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:38]([O:39][C:34](=[O:35])[C:33]([CH2:32][CH3:31])=[C:12]([C:20]([OH:22])=[O:21])[CH2:11][CH2:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][CH:2]([CH3:17])[CH3:1])=[CH:5][C:6]=1[C:14]([OH:16])=[O:15])[CH3:37]

Participants

8

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 7761Diethyl MalonateHCID 8028Tetrahydrofuran2×HCID 20097523HCID 20097523, compound

Product 1

HCID 70202154HCID 70202154, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
-1.5 °C

Procedure

A mixture of 25.7 ml (45.14 g, 0.238 mol) of TiCl4 in 57 ml CCl4 was added dropwise to 475 ml of mechanically-stirring THF that had been cooled to -1.5° C. The mechanical stirring and dropwise addition were done to keep the temperature <3.5° C. The resulting yellow suspension was slowly combined with a second mixture of 27.8 grams (0.119 mol) of 3-(4-(2,2-dimethylethyl)carboxyphenyl)-1-propanal and 19 grams (0.119 mol) of diethyl malonate in 57 ml of dry THF. The combination is performed slowly to maintain a temperature <3° C. At this point, 38.3 ml (37.7 g, 0.476 ml) of dry pyridine were added to the newly combined mixtures This was stirred for 1 hour at 0°-3° C. and then allowed to come to room temperature overnight. The next day the mixture was mixed with 750 ml of water and extracted with 300 ml of ether. The aqueous phase was extracted with ether (2×250 ml) and the extracts were combined. The combined extracts were consecutively washed with 250 ml portions of water, 0.5 N HCl, water, saturated NaHCO3, saturated NaCl and finally dried (Na2SO4). Evaporation of the solvent gave 43.3 grams (97%) of 2-ethylcarboxy-5-(4-(2,2-dimethylethyl)carboxyphenyl)-2-pentenoic acid ethyl ester as an oil, 85.7% pure (HPLC). Selected data: 1H NMR (CDCl3) δ 7.90 (d, J=8.1 Hz, 2H), 7 21 (d, J=8.1 Hz, 2H), 6.97 (t, J =8.4 Hz, 1H), 4.24 (m, 4H), 2.83 (t, J=7.1 Hz, 2H), 2.64 (t, J=7.1 Hz, 2H), 1.57 (s, 9H), 1.26 (m, 6H); IR (CHC13) 1710 cm-1, MS(FD) m/z 377 (M+). An analytical sample was prepared by flash chromatography (hexane - ethyl acetate 8:2). Anal. Calcd for C21H28O6 : C, 67.00; H, 7.50. Found: C, 67.06; H, 7.58.

Workup

  1. additiondropwise addition
  2. customthe temperature <3.5° C
  3. temperatureto maintain a temperature <3° C
  4. stirringThis was stirred for 1 hour at 0°-3° C.
  5. extractionextracted with 300 ml of ether
  6. extractionThe aqueous phase was extracted with ether (2×250 ml)
  7. washThe combined extracts were consecutively washed with 250 ml portions of water, 0.5 N HCl, water, saturated NaHCO3, saturated NaCl
  8. dry with materialfinally dried (Na2SO4)
  9. customEvaporation of the solvent

Sources & evidence

ORD record
ord-e247df0ca772413f8991b632e9a3636b
Source dataset
uspto-grants-1994_04
Patent number
US05302722

Reaction notes

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