تفاعل #358509

ord-ffb09046356649d09786b48e0b4872cb

معادلة التفاعل

CC1(C)CCC(O[SiH3])(c2cccc3c2C(=O)NC3=O)C(C(C)(C)C)C1
4-(tert-butyl-dimethyl-silyloxy-cyclohexyl)-isoindole-1,3-dione
CC1(C)CCC(O[SiH3])(c2cccc3c2C(=O)NC3=O)C(C(C)(C)C)C1
Compound 2
CC1(C)CCC(O[SiH3])(c2cccc3c2C(=O)NC3=O)C(C(C)(C)C)C1
4-(tert-butyl-dimethyl-silyloxy-cyclohexyl)-isoindole-1,3-dione
CC[SiH](CC)CC
triethylsilane
[Br][Bi]([Br])[Br]
bismuth tribromide
O=CCc1ccccc1
phenyl acetaldehyde
O=C1c2ccccc2C(=O)N1[C@H]1CC[C@H](OCCc2ccccc2)CC1
product
O=C1c2ccccc2C(=O)N1[C@H]1CC[C@H](OCCc2ccccc2)CC1
trans-2-(4-Phenylethyloxy-cyclohexyl)-isoindole-1,3-dione

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىbelow 25° C.
  2. 2
    أخرىthe reaction was quenched with 50 mL of saturated sodium bicarbonate
  3. 3
    استخلاصextracted with 3×150 mL portions of ethyl acetate
  4. 4
    تجفيفThe combined extracts were dried over magnesium sulfate
  5. 5
    تركيزconcentrated under reduced pressure

الإجراء التجريبي

To a solution of 10 g of ethyl phenylacetate in 100 mL of dry toluene cooled to −78° C. under nitrogen was added drop-wise 68 mL of 0.9 M di-isobutyl-aluminum hydride in toluene, keeping the internal temperature below −68° C. When the addition was complete, the reaction was quenched with 200 mL of 10% HCl, and extracted into 2×100 mL portions of ether. The combined ether layers were washed with 2×100 mL portions of 10% HCl, 100 mL of saturated sodium bicarbonate, diluted with 100 mL of toluene, and dried over magnesium sulfate. Concentration under reduced pressure gave 7.1 g of phenyl acetaldehyde as a volatile liquid. 1H NMR (400 MHz, CDCl3) 9.8 (s, 1H), 7.5-7.2 (m, 5H), 3.7 (s 2H). To a stirred mixture of 10 g of trans-2-(4-(tert-butyl-dimethyl-silyloxy-cyclohexyl)-isoindole-1,3-dione (Compound 2), 150 mL of anhydrous acetonitrile, 7 mL of triethylsilane and 0.7 g of bismuth tribromide was added 5 g of the freshly prepared phenyl acetaldehyde slowly keeping the temperature at or below 25° C. by means of a cooling bath. After stirring for 2 h, the reaction was quenched with 50 mL of saturated sodium bicarbonate and extracted with 3×150 mL portions of ethyl acetate. The combined extracts were dried over magnesium sulfate and concentrated under reduced pressure. Chromatography over silica gel eluting with a gradient of 2%-25% ethyl acetate in hexane gave 9.0 g of product as a white crystalline solid: 1H NMR (400 MHz, CDCl3) 7.8 (m, 2H), 7.7 (m, 2H), 7.3-7.1 (m, 5H), 4.15 (m, 1H), 3.7 (t, 2H), 3.38 (m, 1H), 2.9 (t, 2H), 2.22 (d, 2H), 2.3 (dd, 2H), 2.18 (d, 2H), 1.78 (d, 2H), 1.4 (dd, 2H).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07452893B2uspto-grants-2008_11