Water → ethyl [(1S)-5-(2,2-diethoxyethoxy)-2,3-dihydro-1H-inden-1-yl]acetate

HRID 2235911Notes

Reaction equation

HRID 2235911 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([OH:15])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2].[CH2:17]([O:19][CH:20]([O:23][CH2:24][CH3:25])[CH2:21]Br)[CH3:18].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[CH2:17]([O:19][CH:20]([O:23][CH2:24][CH3:25])[CH2:21][O:15][C:11]1[CH:10]=[C:9]2[C:14](=[CH:13][CH:12]=1)[C@H:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:16])[CH2:7][CH2:8]2)[CH3:18]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 59300555ethyl [(1S)-5-(2,2-diethoxyethoxy)-2,3-dihydro-1H-inden-1-yl]acetateYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 6, 1.55 g, 7.04 mmol) and bromoacetaldehyde diethyl acetal (4.85 g, 24.6 mmol) in DMF (10 mL) was added Cs2CO3 (2.75 g, 8.44 mmol) followed by water (5 mL). The reaction mixture was heated to reflux for 5 h, cooled to rt, and stirred for 18 h. The solvents were then evaporated under reduced pressure and the residue was dissolved in EtOAc. The organic solution was washed with water, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography to afford the product (1.62 g, 68%) containing minor impurites. 1H NMR (400 MHz, CDCl3) δ 1.21-1.29 (m, 9H) 1.72-1.78 (m, 1H), 2.35-2.48 (m, 2H), 2.74-2.89 (m, 3H), 3.53-3.78 (m, 7H), 4.16 (d, 2H), 4.69 (t, 1H), 6.71 (d, 1H), 6.78 (s, 1H) 7.05 (d, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 5 h
  3. customThe solvents were then evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in EtOAc
  5. washThe organic solution was washed with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-bad480467a444939a3f036e47ecb311f
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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