1-Iodopropane → HCID 22596140, compound

HRID 2054720Notes

Reaction equation

HRID 2054720 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH:17]([N-]C(C)C)([CH3:19])[CH3:18].[Li+].ICCC.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.C(OCC)(=O)C.CCCCCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11](=[O:16])[CH:12]([CH2:18][CH2:17][CH3:19])[CH2:13][CH2:14][CH3:15])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

8

Reactant 4

HCID 336431-IodopropaneHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamideHCID 135552471-(3,4-Dimethoxyphenyl)pentan-1-one2×

Product 1

HCID 22596140HCID 22596140, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

3′,4′-Dimethoxyvalerophenone. 3′,4′-Dimethoxyvalerophenone (9.91 grams, 55 mmol) was added over 20 minutes to a cooled (0° C.) stirred solution of lithium diisopropylamide (28.9 milliliters, 2M, 57.8 mmol). After an additional 5 minutes the solution was cooled to −78° C. and 1-iodopropane (10.73 milliliters, 110 mmol) was rapidly added. The solution was allowed to slowly warm to room temperature and stirring was continued for 3 days. Reaction progress was monitored by TLC (30%, ethyl acetate/hexane, UV) and an equilibrium had been reached after three days between starting material (Rf=0.15), monoalkylated product (Rf=0.32) and dialkylated product (Rf=0.42). The reaction was treated with water (60 milliliters), ethyl acetate (100 milliliters) and a saturated solution of sodium bicarbonate (100 milliliters). The organic layer was separated and washed successively with 5% hydrochloric acid (100 milliliters) and saturated aqueous sodium bicarbonate (100 milliliters). The organic layer was dried over magnesium sulfate and concentrated to afford 15.17 grams of crude product as an orange oily liquid. The crude product was purified by flash chromatography (silica gel, 20% ethyl acetate/hexane) to afford 3.68 (25%) of the dialkylated product (3′,4′-dimethoxy-2-propylvalerophenone) as a yellow solid and 1.01 grams (8%) of the monoalkylated product (3′,4′-dimethoxyvalerophenone) as a yellow oily liquid: 1H NMR (CDCl3) δ 7.65-7.50 (m, 2H), 6.95-6.85 (m, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 2.99-2.88 (m, 2H), 1.52-1.34 (m, 2H), 1.04-0.91 (m, 3H); 13C NMR (CDCl3), δ 199.1, 152.9, 148.8, 130.2, 122.5, 110.0, 109.8, 55.9, 55.8, 37.7, 26.7, 22.4, 13.8.

Workup

  1. temperatureAfter an additional 5 minutes the solution was cooled to −78° C.
  2. temperatureto slowly warm to room temperature
  3. customReaction progress
  4. waitan equilibrium had been reached after three days
  5. customThe organic layer was separated
  6. washwashed successively with 5% hydrochloric acid (100 milliliters) and saturated aqueous sodium bicarbonate (100 milliliters)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated
  9. customto afford 15.17 grams of crude product as an orange oily liquid
  10. customThe crude product was purified by flash chromatography (silica gel, 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9f03c29741d04d718e8248fcb2a8883c
Source dataset
uspto-grants-2008_02
Patent number
US07329761B2

Reaction notes

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