Sodium hydride → HCID 54413351, compound

HRID 1086807Notes

Reaction equation

HRID 1086807 reaction equation
C(OP([CH2:9][C:10]([O:12][CH3:13])=[O:11])(OCC)=O)C.[H-].[Na+].[C:16]([C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:29][CH3:30])[CH:25]=2)[CH:20]=1)(=O)[CH3:17].[NH4+].[Cl-]>C1COCC1.O>[CH3:30][O:29][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[CH:20]=[C:19]([C:16]([CH3:17])=[CH:9][C:10]([O:12][CH3:13])=[O:11])[CH:28]=[CH:27]2

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 66113Methyl diethylphosphonoacetateHCID 775062-Acetyl-6-methoxynaphthalene

Product 1

HCID 54413351HCID 54413351, compoundYield 58.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl diethylphosphonoacetate (1.6 g, 7 5 mmol) and NaH (0.19 g, 7.5 mmol) in THF (25 mL) was added to 2-acetyl-6-methoxynaphthalene (1.5 g, 7.5 mmol) in THF (50 mL) at 23° C. under nitrogen. After refluxing for 20 hours, the reaction mixture was cooled, saturated NH4Cl added, and the mixture poured into water. The solution was extracted with ether and the organic extracts were dried (MgSO4) and the solvent evaporated. Chromatography (silica gel, ether/pentane) afforded methyl 3-(6-methoxy-2-naphthyl)-2-butenoate (0.75 g). This intermediate (0.51 g, 2 mmol) in methanol (50 mL) was hydrogenated with 20% Pd/C (50 mg) at 3 atm at 23° C. until the theoretical amount of hydrogen was taken up. Removal of solvent and catalyst gave the crude ester which was dissolved in isopropanol/water : 2/1 (40 mL). Lithium hydroxide (82 mg, 2 mmol) was added and the reaction mixture stirred at 23° C. for 1 hour. Saturated ammonium chloride was added and the mixture extracted with ethyl acetate. Removal of solvent followed by recrystallization from methanol/water gave 3-(6-methoxy-2-naphthyl) butyric acid (0.45 g). Bromine (3 mL of a 1M solution in CCl4, 3 mmol) was added slowly to the acid (0.37 g, 1.5 mmol) and PBr3 (0.4 g, 1.5 mmol) in CCl4 (20 mL) at 23° C. under nitrogen. The mixture was heated at 80° C. for 20 hours. The mixture was then cooled and poured into ice water. Extraction with benzene followed by drying (Na2SO4) and evaporation gave a crude residue which was distilled under reduced pressure (0.5 mm) to afford 2-bromo-3-(6-methoxy-2-naphthyl)butyrylbromide (0.55 g). 1H NMR(60 MHz, DMSO-d6): 1.30 (3H, d J=7 Hz), 3.80 (3H, s), 4.01 (1H, g, J=7 Hz), 4.20 (1H, d, J=7 Hz), 7.0-8.0 (6H, m); Mass Spectrum: 386(M+).

Workup

  1. temperatureAfter refluxing for 20 hours
  2. temperaturethe reaction mixture was cooled
  3. extractionThe solution was extracted with ether
  4. dry with materialthe organic extracts were dried (MgSO4)
  5. customthe solvent evaporated

Sources & evidence

ORD record
ord-b82c8cd695cc4aebab69599f858258c9
Source dataset
uspto-grants-1991_07
Patent number
US05032588

Reaction notes

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