تفاعل #2058114

معادلة التفاعل

pyridinium tribromide

methyl 3-cyclohexyl-1H-indole-6-carboxylate

→

1H-indole-6-carboxylic acid

المذيبات

CHCl3 THF

ظروف التفاعل

المعالجة

1. 1
   غسيلwashed with sat. aq. NaHSO3 (1 L), 1N HCl (1 L) and brine (1 L)
2. 2
   تجفيفThe organic layer was dried (MgSO4)
3. 3
   تركيزconcentrated
4. 4
   workup.ADDITIONThe resulting red oil was diluted with Et2O
5. 5
   تركيزconcentrated
6. 6
   workup.DISSOLUTIONThe resulting pink solid was dissolved into Et2O (200 mL)
7. 7
   workup.ADDITIONtreated with hexanes (300 mL)
8. 8
   تركيزpartially concentrated
9. 9
   ترشيحThe solids were collected by filtration
10. 10
    غسيلrinsed with hexanes
11. 11
    تركيزThe mother liquor was concentrated to dryness

الإجراء التجريبي

Freshly recrystallized pyridinium tribromide (recrystallization from hot AcOH (5 mL per 1 g), rinsed with cold AcOH and dried under high vacuum over KOH) was added in portions (over 10 min.) to a stirring solution of methyl 3-cyclohexyl-1H-indole-6-carboxylate (60 g, 233 mmol) (prepared using procedures describe in WO2004/065367) in CHCl3/THF (1:1, 1.25 L) at 2° C. The reaction solution was stirred at 0-5° C. for 2.5 h, and washed with sat. aq. NaHSO3 (1 L), 1N HCl (1 L) and brine (1 L). The organic layer was dried (MgSO4) and concentrated. The resulting red oil was diluted with Et2O and concentrated. The resulting pink solid was dissolved into Et2O (200 mL) treated with hexanes (300 mL) and partially concentrated. The solids were collected by filtration and rinsed with hexanes. The mother liquor was concentrated to dryness and the procedure repeated. The solids were combined to yield 1H-indole-6-carboxylic acid, 2-bromo-3-cyclohexyl-, methyl ester (64 g, 190 mmol, 82%) as a fluffy pink solid, which was used without further purification. 1H NMR (300 MHz, CDCl3) δ 1.50-1.27 (m, 3H), 1.98-1.72 (m, 7H), 2.82 (tt, J=3.7, 11.7 Hz, 1H), 3.92 (s, 3H), 7.69 (d, J=8.8 Hz, 1H), 7.74 (dd, J=1.4, 8.8 Hz, 1H), 8.03 (d, J=1.4 Hz, 1H), 8.47 (br s, 1H). 13C NMR (75 MHz, CDCl3) δ 26.1, 27.0 (2), 32.2 (2), 37.0, 52.1, 110.7, 112.8, 118.7, 120.3, 120.8, 123.1, 130.2, 135.6, 168.2. LCMS: m/e 334 (M−H)−, ret time 3.34 min., 4 minute gradient. Stop time: 5 minutes; Gradient time: 4 minutes; Starting conc: 0% B; Ending conc: 100% B; Eluent A: 5% CH3CN/95% H2O with 10 mM NH4OAc; Eluent B: 95% CH3CN/5% H2O with 10 mM NH4OAc; Column: Phenomenex 10μ 4.6×50 mm C18.

المصدر