Methanol → 6-Methoxy-1-Indanone

HRID 971066Notes

Reaction equation

HRID 971066 reaction equation
C[C:2]([OH:5])([CH3:4])[CH3:3].[CH3:6][OH:7].[C:8]1([CH3:14])C=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH3:6][O:7][C:11]1[CH:12]=[C:4]2[C:8]([CH2:14][CH2:3][C:2]2=[O:5])=[CH:9][CH:10]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1140Toluene2×HCID 6386tert-Butanol2×

Product 1

HCID 3340366-Methoxy-1-IndanoneYield 80%

Procedure

An oven-dried flask was charged with β-keto methyl ester (1.0 mmol), Bu2SnO (26 mg, 0.1 mmol, 0.1 eq.), tBuOH (5 mL) and toluene (15 mL). The flask was connected a Dean-Star trap which continuingly removed methanol while refluxing. tBuOH (2 mL) was added when the mixture of alcohols and toluene was released through Dean-Star trap. The mixture was refluxed for 4 hours. The resultant yellow solution was concentrated on a water evaporator. The residue was directly loaded on silica gel column for purification (hexanes/EtOAc 20/1) to give β-keto tButylester (80-84% yield) as a white solid (6-methoxyindanone) and a purple solid (5-chloroindanone), respectively. For 5-chloroindanone ester (84%) 22D: 1H NMR (CDCl3, 400 MHz) (85% keto ester form): δ ppm 7.68 (d, J=8.0 Hz, 1H), 7.49 (s, 1H), 7.36 (d, J=8.0 Hz, 1H), 3.63 (dd, J=8.0, 4.0 Hz, 1H), 3.48 (dd, J=17.2, 4.0 Hz, 1H), 3.31 (dd, J=17.2, 4.0 Hz, 1H), 1.49 (s, 9H). (15% enol form): δ ppm 10.25 (br s, 1H), 7.53 (d, J=7.6 Hz, 1H), 7.42 (s, 1H), 7.35 (d, J=7.6 Hz, 1H), 3.46 (s, 2H), 1.57 (s, 9H). 3C NMR (CDCl3, 100 MHz) (keto and enol forms): δ ppm 198.46, 167.85, 155.07, 141.77, 133.88, 128.50, 127.18, 126.70, 125.59, 125.01, 121.38, 82.28, 54.39, 32.71, 29.99, 28.42, 27.96. FT-IR (ν, cm−1): 2980 (m), 2933 w), 1716 (s, with a shoulder at 1745), 1649 (m), 1601 (m), 1369 (m), 1260 (m), 1154 (s). For 6-methoxyindanone ester (80%) 22C: 1H NMR (CDCl3, 400 MHz) (90% keto ester form): δ ppm 7.38 (d, J=8.0 Hz, 1H), 7.20 (m, 2H), 3.83 (s, 3H), 3.64 (dd, J=8.0, 3.6 Hz, 1H), 3.40 (dd, J=16.8, 3.6 Hz, 1H), 3.26 (dd, J=16.8, 8.0 Hz, 1H), 1.49 (s, 9H). (10% enol form): δ ppm 10.52 (br s, 1H), 7.32 (d, J=8.4 Hz, 1H), 7.13 (d, J=2.0 Hz, 1H), 6.96 (dd, J=8.4, 2.0 Hz, 1H), 3.85 (s, 3H), 3.40 (s, 2H), 1.57 (s, 9H). 13C NMR (CDCl3, 100 MHz) (keto and enol forms): δ ppm 199.94, 168.32, 159.53, 146.53, 136.56, 127.11, 124.64, 105.48, 81.92, 55.53, 55.04, 29.62, 28.41, 27.94. FT-IR (ν, cm−1): 2980 (m), 1709 (s, with a shoulder at 1740), 1645 (m), 1494 (m), 1277 (m), 1149 (s), 1028 (m).

Workup

  1. temperaturewhile refluxing
  2. temperatureThe mixture was refluxed for 4 hours
  3. concentrationThe resultant yellow solution was concentrated on a water evaporator
  4. customThe residue was directly loaded on silica gel column for purification (hexanes/EtOAc 20/1)

Sources & evidence

ORD record
ord-63584f71806c4a18897fa3abc8bdd6d3
Source dataset
uspto-grants-2007_12
Patent number
US07312335B2

Reaction notes

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