Carbon Dioxide → 1-(tert-butyldimethylsilyl)-5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid

HRID 493151Notes

Reaction equation

HRID 493151 reaction equation
[Li]C(C)(C)C.CCCCC.Br[C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[CH:19]=2)[N:14]([Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH:13]=1.[C:35](=[O:37])=[O:36]>C1COCC1>[C:31]([Si:28]([CH3:30])([CH3:29])[N:14]1[C:15]2=[N:16][CH:17]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[CH:19]=[C:20]2[C:12]([C:35]([OH:37])=[O:36])=[CH:13]1)([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 280Carbon Dioxide2×HCID 8003PentaneHCID 576811263-bromo-1-(tert-butyldimethylsilyl)-5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 576811381-(tert-butyldimethylsilyl)-5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acidYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1.7 M solution of t-BuLi in pentane (24.8 mL, 42.2 mmol) was added dropwise over a period of 25 min to a stirred and cooled (−78° C.) solution of 9 (8.20 g, 20.3 mmol) in THF (93 in L) at such a rate that the temperature did not exceed −65° C. After the addition, the mixture was stirred for 1 h at −78° C. Dry gaseous CO2 was introduced to the flask over a period of 10 min (exothermic reaction, external dry ice bath). When the exothermic reaction subsided, cooling bath was removed, and the mixture was allowed to reach 0° C. The mixture was then separated between brine-AcOEt. The aqueous layer was extracted with AcOEt (2×). Combined organic solutions were dried dried (MgSO4), concentrated and purified by SGC with CH2Cl2:AcOEt as eluent in gradient (up to 12% AcOEt) to afford 10 (5.74 g, 76%) as tan solid. 1H NMR (400 MHz, CDCl3) δ 0.71 (s, 6H), 0.99 (s, 9H), 7.05-7.12 (m, 1H), 7.37-7.42 (m, 1H), 7.43-7.50 (m, 2H), 8.11 (s, 1H), 8.58 (d, J=2.3 Hz, 1H), 8.61 (d, J=2.3 Hz, 1H).

Workup

  1. customdid not exceed −65° C
  2. additionAfter the addition
  3. stirringthe mixture was stirred for 1 h at −78° C
  4. customWhen the exothermic reaction
  5. temperaturecooling bath
  6. customwas removed
  7. customto reach 0° C
  8. customThe mixture was then separated between brine-AcOEt
  9. extractionThe aqueous layer was extracted with AcOEt (2×)
  10. customCombined organic solutions were dried
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. custompurified by SGC with CH2Cl2

Sources & evidence

ORD record
ord-30731bed595c4561ba47fc2cd2484a38
Source dataset
uspto-grants-2009_05
Patent number
US07534800B2

Reaction notes

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