Dimethyl Carbonate → (1S-trans)-Methyl 1-(1,3-benzodioxol-5-yl)-2,3-dihydro-3-oxo-5-propoxy-1H-indene-2-carboxylate

HRID 277494Notes

Reaction equation

HRID 277494 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C@H:10]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=4)[C:12](=[O:23])[CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[C:24](=O)([O:27]C)[O:25][CH3:26]>C(O)(=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C@H:10]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=4)[C:12](=[O:23])[C@@H:11]3[C:24]([O:25][CH3:26])=[O:27])=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

4

Reactant 2

HCID 12021Dimethyl CarbonateHCID 11833850(S)-3-(1,3-Benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-inden-1-one

Product 1

HCID 18683602(1S-trans)-Methyl 1-(1,3-benzodioxol-5-yl)-2,3-dihydro-3-oxo-5-propoxy-1H-indene-2-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

A 250 mL three-necked flask under nitrogen was charged with (S)-3-(1,3-Benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-inden-1-one (6.6 g, 21.3 mmol, 90% e.e.) and dimethyl carbonate (70 mL). To the solution was added sodium t-amylate (4.7 g, 42.5 mmol) in four portions over 20 minutes to maintain the temperature below 35° C. Upon complete addition of base, stir the solution until the temperature drops to 20° C. (˜1.5 h). Cool the solution to 0° C. and add a 50% acetic acid solution (50 mL) over 15 minutes to keep the temperature below 5° C. Concentrate the solution to ¼ volume, add toluene (100 mL), wash the organic phase with water (2×100 mL), sat. NaHCO3 (100 mL), brine (100 mL), dry over MgSO4 and concentrate in vacuo. Slurry the crude solid in cold MeOH (25 mL, 0° C.), filter and air dry to afford (1S-trans)-Methyl 1-(1,3-benzodioxol-5-yl)-2,3-dihydro-3-oxo-5-propoxy-1H-indene-2-carboxylate as a pale yellow solid (4.8 g, 62%): mp 103.0-105.5° C.; 1H NMR δ7.15 (d, J=2.3 Hz, 1H), 7.05 (d, J=8.4 Hz, 1H), 6.95 (dd, J=2.4, 8.3 Hz, 1H), 6.7 (m, 2H), 6.45 (d, J=1.2 Hz, 1H), 6.4 (m, 2H), 4.6 (s, 1H 3.9 (t, J=6.5 Hz, 2H), 3.7 (s, 3H), 1.8 (quintet, J=7.2 Hz, 2H), 1.05 (t, J=7.4 Hz, 3H).

Workup

  1. temperatureto maintain the temperature below 35° C
  2. additionUpon complete addition of base
  3. customdrops to 20° C.
  4. custom(˜1.5 h)
  5. customthe temperature below 5° C
  6. concentrationConcentrate the solution
  7. additionadd toluene (100 mL)
  8. washwash the organic phase with water (2×100 mL), sat. NaHCO3 (100 mL), brine (100 mL)
  9. dry with materialdry over MgSO4
  10. concentrationconcentrate in vacuo
  11. customsolid in cold MeOH (25 mL, 0° C.)
  12. filtrationfilter
  13. customair dry

Sources & evidence

ORD record
ord-c420dfeb67ca4b53856cd791e53680a6
Source dataset
uspto-grants-2002_03
Patent number
US06355813B1

Reaction notes

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