Реакция #2286897

Уравнение реакции

mixture

ethyl 3-(3-hydroxypropyl)-7-(2-methoxyphenyl)-1H-indole-2-carboxylate

2-methyl-1-naphthol

triphenylphosphine

di-tert-butyl azodicarboxylate

HCl

LiOH

→

7-(2-methoxyphenyl)-3-(3-((2-methyl-1-naphthyl)oxy)propyl)-1H-indole-2-carboxylic acid

Растворители

THF

water

THF

methanol

Условия реакции

Обработка

1. 1
   Другоеpartitioned between ethyl acetate (150 mL) and water (50 mL)
2. 2
   ПромывкаThe organic layer was washed with brine
3. 3
   Сушкаa dried (Na2SO4)
4. 4
   Фильтрацияfiltered
5. 5
   Концентрированиеconcentrated
6. 6
   ДругоеThe concentrate was purified by flash chromatography on silica gel with 5% ethyl acetate in hexanes
7. 7
   Другоеto provide an intermediate which
8. 8
   Экстракцияextracted with ethyl acetate
9. 9
   ПромывкаThe extract was washed with water and brine
10. 10
    Сушкаdried (Na2SO4)
11. 11
    Фильтрацияfiltered
12. 12
    Концентрированиеconcentrated
13. 13
    ДругоеThe concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA)

Методика

To a mixture of EXAMPLE 47A (71 mg), 2-methyl-1-naphthol (35 mg), triphenylphosphine (58 mg) in THF (2 mL) and di-tert-butyl azodicarboxylate (55 mg) was stirred at ambient temperature overnight and partitioned between ethyl acetate (150 mL) and water (50 mL). The organic layer was washed with brine and a dried (Na2SO4), filtered and concentrated. The concentrate was purified by flash chromatography on silica gel with 5% ethyl acetate in hexanes to provide an intermediate which was dissolved in THF (2 mL), methanol (1 mL) and water (1 mL) and hydrolyzed with LiOH (100 mg) overnight. The mixture was acidified with 5% HCl and extracted with ethyl acetate. The extract was washed with water and brine and dried (Na2SO4), filtered and concentrated. The concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA). 1H NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 8.12 (dd, 1H), 7.82 (d, 1H), 7.77 (d, 1H), 7.52 (d, 1H), 7.36-7.47 (m, 5H), 7.27 (d, 1H), 7.09 (t, 2H), 4.10 (t, 2H), 3.83 (s, 3H), 3.48 (t, 2H), 2.46 (s, 3H), 2.38 (m, 2H).

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