Potassium Phosphate, Tribasic → tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-chloro-3-quinolinyl)-1H-indole-1-carboxylate

HRID 381752Notes

Reaction equation

HRID 381752 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:28][C:29]1[C:38](I)=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:18]([O:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:9]([C:38]1[C:29]([Cl:28])=[N:30][C:31]3[C:36]([CH:37]=1)=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:10]2)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 146166232-Chloro-3-iodoquinolineHCID 22285134[1-(tert-Butoxycarbonyl)-5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indol-2-yl]boronic acid

Product 1

HCID 17930066tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-chloro-3-quinolinyl)-1H-indole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A deoxygenated mixture of 1-(tert-butoxycarbonyl)-5-{[tert-butyl(dimethyl)silyl[oxy}-1H-indol-2-ylboronic acid 1-6 (4.10 g, 10.5 mmol, 1 equiv), 2-chloro-3-iodo-quinoline (1-2, 3.64 g, 12.6 mmol, 1.20 equiv), potassium phosphate (6.67 g, 31.4 mmol, 3.00 equiv), and tetrakis(triphenylphosphine)palladium (0.605 g, 0.524 mmol, 0.050 equiv) in dioxane (100 mL) was heated at 90° C. for 20 h. The reaction mixture was cooled, then partitioned between a mixture of water and ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by flash column chromatography (20% dichloromethane in hexanes, grading to 90% dichloromethane in hexanes) to give tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-chloro-3-quinolinyl)-1H-indole-1-carboxylate (1-7) as a tan-colored foam. 1H NMR (400 MHz, CDCl3) δ8.16 (s, 1H), 8.15 (d, 1H, J=9.0 Hz), 8.07 (d, 1H, J=8.2 Hz), 7.86 (d, 1H, J=7.8 Hz), 7.77 (br t, 1H, J=8.4 Hz), 7.60 (br t, 1H, J=8.1 Hz), 7.03 (d, 1H, J=2.4 Hz), 6.92 (dd, 1H, J=9.0, 2.4 Hz), 6.55 (s, 1H), 1.26 (s, 9H), 1.02 (s, 9H), 0.23 (s, 6H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between a mixture of water and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (20% dichloromethane in hexanes, grading to 90% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-629f2c3bd71a49de9c9f1099d627032c
Source dataset
uspto-grants-2001_10
Patent number
US06306874B1

Reaction notes

Loading…