Imidazole → HCID 21099201, compound

HRID 1351736Notes

Reaction equation

HRID 1351736 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[C:4]1[CH2:15][CH2:14][O:13][C:12]([CH2:19][CH2:20][OH:21])([CH2:16][CH2:17][CH3:18])[C:5]=1[NH:6]2.N1C=CN=C1.[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[C:4]1[CH2:15][CH2:14][O:13][C:12]([CH2:19][CH2:20][O:21][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])([CH2:16][CH2:17][CH3:18])[C:5]=1[NH:6]2

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 21099144HCID 21099144, compound

Product 1

HCID 21099201HCID 21099201, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5-bromo-8-fluoro-1-propyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acid ethyl ester (2.0 g, 5.02 mmol) in THF (10 mL) was added LAH (5.27 mL of 1.0 M in THF, 5.27 mmol) slowly at room temperature. The mixture was stirred for 30 minutes at room temperature. The reaction mixture was quenched by the addition of H2O (0.5 mL) and then 10% NaOH (0.5 mL) was added to the mixture. Na2SO4 was added to the mixture and the resulting mixture was filtered. The filtrate was concentrated to give 1.79 g (100%) of 2-(5-bromo-8-fluoro-1-propyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-ethanol as yellow oil. A mixture of 2-(5-bromo-8-fluoro-1-propyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-ethanol (1.79 g, 5.02 mmol), imidazole (0.854 g, 12.55 mmol) and tert-butyldimethylsilyl chloride (0.909 g, 6.03 mmol) in DMF (10 mL) was stirred overnight at room temperature. The reaction mixture was diluted with EtOAc (100 mL). The organic solution was washed with H2O (5×100 mL) and brine (100 mL), dried (Na2SO4), and concentrated. The residue was purified by flash chromatography (silica, 7% EtOAc in hexanes) to give 2.29 g (97%) of title compound as a white solid. 1H NMR (CDCl3): 300 MHz δ 8.97 (bs, 1H), 6.95 (dd, J=8.37, 4.17 Hz, 1H), 6.57 (d, J=10.41, 8.37 Hz, 1H), 3.98–3.54 (m, 4H), 3.00 (m, 2H), 2.00–0.90 (m, 6H), 0.80 (s, 9H), 0.74 (d, J=7.32 Hz, 3H), 0.06 (s, 3H), 0.03 (s, 3H).

Workup

  1. washThe organic solution was washed with H2O (5×100 mL) and brine (100 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography (silica, 7% EtOAc in hexanes)

Sources & evidence

ORD record
ord-66f7bb8864b34f6cbc3a273dba296b20
Source dataset
uspto-grants-2007_05
Patent number
US07217730B2

Reaction notes

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