Tetrabutylammonium Fluoride → Methyl-7-chloro-3-cyclohexyl-1-(2-hydroxyethyl)-2-(4-methoxyphenyl)-1H-indole-6-carboxylate

HRID 1672147Notes

Reaction equation

HRID 1672147 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]([Cl:14])=[C:12]2[C:8]([C:9]([CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[C:10]([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[N:11]2[CH2:15][CH2:16][O:17][Si](C(C)(C)C)(C)C)=[CH:7][CH:6]=1)=[O:4].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:13]([Cl:14])=[C:12]2[C:8]([C:9]([CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[C:10]([C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[N:11]2[CH2:15][CH2:16][OH:17])=[CH:7][CH:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59802484Methyl-1-(2-(tert-butyldimethylsilyloxy)ethyl)-7-chloro-3-cyclohexyl-2-(4-methoxy phenyl)-1H-indole-6-carboxylate

Product 1

HCID 59802496Methyl-7-chloro-3-cyclohexyl-1-(2-hydroxyethyl)-2-(4-methoxyphenyl)-1H-indole-6-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 131 mgs (1 equivalents, 236 μmol) of Methyl-1-(2-(tert-butyldimethyl silyloxy)ethyl)-7-chloro-3-cyclohexyl-2-(4-methoxy phenyl)-1H-indole-6-carboxylate in 4 mL of THF was added under N2 a 1 M solution of tetrabutylammonium fluoride in THF (2 equivalents, 471 μL). The reaction mixture was stirred for two hours at room temperature. The solution was concentrated en vacuo, washed with water and the product extracted with ethyl acetate. Automated flash chromatography (Biotage Horizon™, gradient elution, 10 to 50% Ethyl Acetate/Hexane) gave 97.0 mgs (93%) of Methyl-7-chloro-3-cyclohexyl-1-(2-hydroxyethyl)-2-(4-methoxyphenyl)-1H-indole-6-carboxylate. The LC/MS data was obtained on a Shimadzu analytical LC/Micromass Platform LC (ESI+) at 220 nm using the following set of conditions: Phenomenex 10 μm C18, 4.6×30 mm column, with a gradient of 0-100% B (B=90% HPLC grade methanol/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade methanol), in 2 minutes with a 1 minute hold at a rate of 5 mL/minute. The NMR spectra was recorded at room temperature using a Bruker DRX300 spectrometer. Chemical shifts were reported in ppm relative to the deuterated solvent used. Coupling constants were reported in hertz. Peak multiplicity was reported using the following abbreviations: s (singlet), d (doublet), dd (doublet of doublets), t (triplet), m (multiplet), br (broad). 1H NMR (300 MHz, CDCl3) δ 7.67 (d, J=8.42 Hz, 1H), 7.50 (d, J=8.42 Hz, 1H), 7.25 (d, J=8.78 Hz, 2H), 7.01 (d, J=8.78 Hz, 2H), 4.50 (t, J=6.22 Hz, 2H) 3.94 (s, 3H), 3.89 (s, 3H), 3.76 (t, J=6.22 Hz, 2H), 2.55 (m, 1H), 1.71 (m, 6H) 1.38 (m, 1H) 1.23 (m, 3H). MS m/z 442.15 (M+H), Rf 2.20 min., 96.4% purity.

Workup

  1. concentrationThe solution was concentrated en vacuo
  2. washwashed with water
  3. extractionthe product extracted with ethyl acetate
  4. washAutomated flash chromatography (Biotage Horizon™, gradient elution, 10 to 50% Ethyl Acetate/Hexane)

Sources & evidence

ORD record
ord-796081e2c7514893bde2a51a9ba862be
Source dataset
uspto-grants-2011_08
Patent number
US07998951B2

Reaction notes

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