Ethyl bromoacetate → HCID 70413007, compound

HRID 1248617Notes

Reaction equation

HRID 1248617 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:24])[C:16]3[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=3)[CH:10]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[CH2:9]2)=[CH:4][CH:3]=1.Br[CH2:26][C:27](OCC)=[O:28]>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:24])[C:16]3[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=3)[CH:10]([C:18]3[CH2:23][CH2:22][N:21]([CH:27]([OH:28])[CH3:26])[CH2:20][CH:19]=3)[CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 7748Ethyl bromoacetateHCID 20277029HCID 20277029, compound

Product 1

HCID 70413007HCID 70413007, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
0 °C

Procedure

3-(4'-Fluorophenyl)-3-hydroxy-6-methyl-1-(4-pyridyl)indane (Example 8) (9.0 g) was refluxed with ethyl bromoacetate (5.0 g) in acetone (50 ml) for 3 hrs. The reaction mixture was cooled in a refrigerator overnight and the precipitated pyridinium bromide filtered off. Yield: 7.8 g (56.9%). MP: 177°-78° C. This bromide (7.0 g) was dissolved in methanol (50 ml), cooled to 0° C., and NaBH4 (3.0 g) was added during 1 hour under stirring. The reaction mixture was poured into NH4Cl (10 g) in 1 liter of H2O and finally extracted with ethyl acetate (2×150 ml). The combined organic phases were dried (MgSO4) and the ethyl acetate evaporated. The remaining oil (1-(1-ethylcarboxymethyl-1,2,3,6-tetrahydropyrid-4-yl)-3-(4'-fluorophenyl)-3-hydroxy-6-methylindane) was dissolved in dry tetrahydrofuran (25 ml) and added dropwise to a suspension of LiAlH4 (1.8 g) in dry tetrahydrofuran under ice cooling. The mixture was refluxed for two hours, hydrolysed by careful addition of H2O (5 ml) in tetrahydrofuran (100 ml). The precipitate was filtered off, and the solvent evaporated leaving the title compound as an oil.

Workup

  1. temperatureThe reaction mixture was cooled in a refrigerator overnight
  2. filtrationthe precipitated pyridinium bromide filtered off
  3. dissolutionThis bromide (7.0 g) was dissolved in methanol (50 ml)
  4. additionNaBH4 (3.0 g) was added during 1 hour
  5. additionThe reaction mixture was poured into NH4Cl (10 g) in 1 liter of H2O
  6. extractionfinally extracted with ethyl acetate (2×150 ml)
  7. dry with materialThe combined organic phases were dried (MgSO4)
  8. customthe ethyl acetate evaporated
  9. dissolutionThe remaining oil (1-(1-ethylcarboxymethyl-1,2,3,6-tetrahydropyrid-4-yl)-3-(4'-fluorophenyl)-3-hydroxy-6-methylindane) was dissolved in dry tetrahydrofuran (25 ml)
  10. additionadded dropwise to a suspension of LiAlH4 (1.8 g) in dry tetrahydrofuran under ice cooling
  11. temperatureThe mixture was refluxed for two hours, hydrolysed by careful addition of H2O (5 ml) in tetrahydrofuran (100 ml)
  12. filtrationThe precipitate was filtered off
  13. customthe solvent evaporated

Sources & evidence

ORD record
ord-0b64376b420c4bf294ac405d8c4b31f4
Source dataset
uspto-grants-1985_06
Patent number
US04525360

Reaction notes

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