Sodium Carbonate → HCID 18398758, compound

HRID 1018921Notes

Reaction equation

HRID 1018921 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)=[C:9]1Br)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]([F:43])([F:42])[C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)=[C:9]1[C:31]1[CH:32]=[C:33]([C:35]([F:38])([F:36])[F:37])[CH:34]=[C:29]([C:28]([F:27])([F:43])[F:42])[CH:30]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 1562653,5-Bis-trifluoromethylphenylboronic acidHCID 18398751HCID 18398751, compound

Product 1

HCID 18398758HCID 18398758, compoundYield 79.9%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a degassed solution of 1-tert-butoxycarbonyl-2-bromo-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1H-indole (2.0 g), 3,5-bis(trifluoromethyl)phenylboronic acid (2.43 g) and Na2CO3 (aq., 2N, 8.8 ml) in tetrahydrofuran was added tetrakis(triphenylphosphine)-palladium(0) (0.55 g). The resulting solution was then warmed to reflux for 18 h, cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography (SiO2; 3-5% ethyl acetate/hexanes) to afford the title compound (2.1 g). 1H NMR (CDCl3) δ1.23 (s, 9H), 1.45-1.71 (br m, 6H), 2.82 (t, 2H, J=7.2 Hz), 3.37 (m, 1H), 3.61 (m, 2H), 3.98 (m, 1H), 4.50 (t, 1H, J=3.5 Hz), 7.30 (t, 1H, J=7.0 Hz), 7.41 (t, 1H, J=7.0 Hz), 7.60 (d, 1H, J=10.0 Hz), 7.89 (s, 1H), 7.91 (s, 2H), 8.27 (d, 1H, J=10.0 Hz).

Workup

  1. temperatureThe resulting solution was then warmed
  2. temperatureto reflux for 18 h
  3. custompartitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by flash chromatography (SiO2; 3-5% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4470f5e8310b4f2d883d29eb851774d3
Source dataset
uspto-grants-2002_11
Patent number
US06486153B1

Reaction notes

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