반응 #631981

반응 방정식

2-(3-bromo-2-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole

THF

isopropyl magnesium chloride

isopropyl magnesium chloride

→

2-(3-isopropyl-2-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole

용매

—

hexanes

ether

반응 조건

후처리

1. 1
   기타A dry 3-neck 250 mL round bottom flask equipped
2. 2
   workup.STIRRINGThe reaction was stirred overnight at room temperature, at which point 1H NMR
3. 3
   온도reflux for 3 hours
4. 4
   기타resulted in no further progression of the reaction
5. 5
   온도The mixture was cooled to 15° C.
6. 6
   workup.STIRRINGthe mixture was stirred overnight at room temperature
7. 7
   기타The reaction was quenched with saturated aqueous NH4Cl
8. 8
   기타the organic layer was removed
9. 9
   추출the aqueous layer was extracted
10. 10
    기타dried
11. 11
    기타The solvent was removed in vacuo
12. 12
    기타to yield 3.84 g crude product as a yellow oil

실험 절차

A dry 3-neck 250 mL round bottom flask equipped with magnetic stirring and held under a nitrogen atmosphere was charged with 5.0 g 2-(3-bromo-2-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole, 60 mL anhydrous THF, and 100 mg Ni(dppp)Cl2. The mixture was cooled to 15° C., and isopropyl magnesium chloride (11 mL, 2M in ethyl ether) was added. A mild exotherm took place, and the mixture darkened slightly. The reaction was stirred overnight at room temperature, at which point 1H NMR indicated 50% completion. Addition of ca 75 mg Ni(dppp)Cl2 and reflux for 3 hours resulted in no further progression of the reaction. The mixture was cooled to 15° C., and an additional 13 mL of isopropyl magnesium chloride (2M in ethyl ether) and 100 mg of nickel catalyst were added and the mixture was stirred overnight at room temperature. The reaction was quenched with saturated aqueous NH4Cl, the organic layer was removed, the aqueous layer was extracted, and the organic phases were combined and dried. The solvent was removed in vacuo to yield 3.84 g crude product as a yellow oil. Column chromatography on silica gel using 4:1 hexanes: ether as eluant yielded 0.79 g of 2-(3-isopropyl-2-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole as a colorless oil. 1H NMR (CDCl3, 200 MHz), δ (ppm): 7.5 (d, 1H), 7.37 (d, 1H), 7.22 (t, 1H), 4.13 (s, 2H), 3.23 (m, 1H), 2.5 (s, 3H), 1.45 (s, 6H), 1.22 (d, 6H). The oxazoline was suspended in 34 mL of 6N HCl and refluxed in an oil bath for 6 hours. The mixture was cooled and extracted with CH2Cl2. The extract was dried over Na2SO4 and evaporated to yield 0.76 g of 3-isopropyl-2-methyl-benzoic acid, suitably pure for the next step. 1H NMR (CDCl3, 300 MHz), δ (ppm): 7.8 (d, 1H), 7.48 (d, 1H), 7.3 (t, 1H), 3.3 (m, 1H), 2.55 (s, 3H), 1.2 (d, 6H).

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