Carbon Dioxide → 2-((tert-Butyldimethylsilyloxy)methyl)-1-methyl-1H-indole-5-carboxylic acid

HRID 1481751Notes

Reaction equation

HRID 1481751 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])=[CH:5]2.[Li]CCCC.[C:26](=[O:28])=[O:27]>C1COCC1>[Si:14]([O:13][CH2:12][C:6]1[N:7]([CH3:11])[C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([C:26]([OH:28])=[O:27])=[CH:10][CH:9]=2)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 712845855-bromo-2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-1H-indoleHCID 178418339Butyllithium

Product 1

HCID 712850522-((tert-Butyldimethylsilyloxy)methyl)-1-methyl-1H-indole-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-bromo-2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-1H-indole (5.32 g, 15.0 mmol), prepared according to procedure described in Example 39, Step 3, in THF (30 mL) was added n-BuLi (2.5 M solution in hexanes, 7.30 mL, 18.25 mmol, 1.2 eq) at −78° C. dropwise. The mixture was stirred for 30 min at −78° C. before dry CO2 (g) was bubbled into reaction for 10 min. The reaction was quenched with saturated aqueous NH4Cl then extracted by CH2Cl2 (3×50 mL). The combined organic layers were dried over Na2SO4 then concentrated under reduced pressure to give the title compound (4.80 g, ca. 15.0 mmol) in quantitative yield. The acid was carried over to next step without further purification.

Workup

  1. customwas bubbled into reaction for 10 min
  2. customThe reaction was quenched with saturated aqueous NH4Cl
  3. extractionthen extracted by CH2Cl2 (3×50 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record
ord-1a85251999fd460db08b0ffa853b9fee
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

Loading…