Water → (3-Benzyloxy-2-ethoxyphenyl)-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

HRID 253426Notes

Reaction equation

HRID 253426 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg]Cl)(C)C.[CH2:26]([O:28][C:29]1[C:36]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:35][CH:34]=[CH:33][C:30]=1[CH:31]=[O:32])[CH3:27].O>O1CCCC1>[CH2:38]([O:37][C:36]1[C:29]([O:28][CH2:26][CH3:27])=[C:30]([CH:31]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)[OH:32])[CH:33]=[CH:34][CH:35]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 962WaterHCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 580866452-Ethoxy-3-benzyloxybenzaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 66679415(3-Benzyloxy-2-ethoxyphenyl)-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanolYield 13.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of 3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (68, 1.306 g, 3.26 mmol, prepared as described in Example 22) in tetrahydrofuran (42 mL) at −20° C. under nitrogen was added isopropylmagnesium chloride (1.70 mL, 2.0 M solution in tetrahydrofuran, 3.40 mmol). The reaction mixture was stirred at −20° C. for 1.5 hours. It was allowed to warm to 5° C. and then kept at 5° C. for 1 hour. The reaction mixture was then cooled down to −20° C. To this solution was slowly added a solution of 2-ethoxy-3-benzyloxybenzaldehyde (97, 0.698 g, 2.72 mmol, prepared by protocol of Example 21, Steps 1-3 of Scheme 20, using benzyl bromide in place of 4-chloro-benzyl bromide in Step 1) in tetrahydrofuran (42 mL). The reaction mixture was stirred at −20° C. for 2.5 hrs, and was allowed to warm to 5° C. for 2.5 hours. The reaction mixture was poured into iced water, extracted with ethyl acetate, washed with saturated ammonium chloride and brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as light-yellow oil (98, 200 mg, 13.9%).

Workup

  1. temperatureto warm to 5° C.
  2. waitkept at 5° C. for 1 hour
  3. temperatureThe reaction mixture was then cooled down to −20° C
  4. stirringThe reaction mixture was stirred at −20° C. for 2.5 hrs
  5. temperatureto warm to 5° C. for 2.5 hours
  6. extractionextracted with ethyl acetate
  7. washwashed with saturated ammonium chloride and brine
  8. dry with materialdried over magnesium sulfate
  9. customAfter removal of solvent
  10. customthe residue was purified by silica gel column chromatography
  11. washeluting with ethyl acetate in hexane

Sources & evidence

ORD record
ord-9a25baf067c448a78118047440dd7f3f
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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