Potassium trimethylsilanolate → 13-cyclohexyl-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 273355Notes

Reaction equation

HRID 273355 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:32]([O:34]C)=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:22][CH:23]=[CH:24][N:25]=4)=[CH:18][C:17]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si](C)(C)[O-].[K+]>C1COCC1>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:32]([OH:34])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]4[O:22][CH:23]=[CH:24][N:25]=4)=[CH:18][C:17]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 23668039Potassium trimethylsilanolateHCID 24738409Methyl 13-cyclohexyl-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a] [2]benzazepine-10-carboxylate

Product 1

HCID 2473840813-cyclohexyl-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acidYield 93.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 13-cyclohexyl-3-methoxy-6-(1,3-oxazol-2-yl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate (75.4 mg, 0.16 mMol) was dissolved in 2 mL of THF and potassium trimethylsilanolate (103 mg, 0.80 mMol) added to the reaction. The reaction was stirred at room temperature under a nitrogen atmosphere for 19 hrs. The reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The organic phase was washed sequentially with 1N aqueous hydrochloric acid and brine, dried over magnesium sulfate and volatiles removed in vacuuo to yield 68 mg (93%) of the title product as a yellow solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.18-1.33 (1 H, m), 1.36-1.45 (2 H, m), 1.58 (1 H, br. s.), 1.79 (2 H, d, J=10.07 Hz), 1.96 (1 H, br. s.), 2.08 (3 H, br. s.), 2.88 (1 H, t, J=12.05 Hz), 3.94 (3 H, s), 4.44 (1 H, br. s.), 6.00 (1 H, br. s.), 7.04 (1 H, d, J=2.75 Hz), 7.09 (1 H, dd, J=8.70, 2.59 Hz), 7.31 (1 H, s), 7.56 (1 H, d, J=8.85 Hz), 7.65 (1 H, s), 7.68 (1 H, s), 7.82 (1 H, dd, J=8.55, 1.22 Hz), 7.90 (1 H, d, J=8.55 Hz), 8.54 (1 H, s). HPLC analysis: Shimadzu Analytical HPLC using Discovery VP software: % A=10% methanol, 90% water, 0.1% trifluoroacetic acid; % B=90% methanol, 10% water, 0.1% trifluoroacetic acid; Initial % B=50; Final % B=100; Gradient=5 min; Runtime=6 min; Flow rate=5 ml/min; Wavelength=220 nm; Column=Phenomenex Luna 3.0 mm×50 mm S10. Retention Time=3.83 min, purity 96%. Flow injection Mass Spectrometry: MS m/z 455(MH+), m/z 453(M-H)−.

Workup

  1. customThe reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid
  2. washThe organic phase was washed sequentially with 1N aqueous hydrochloric acid and brine
  3. dry with materialdried over magnesium sulfate and volatiles
  4. customremoved in vacuuo

Sources & evidence

ORD record
ord-a8e9fc18ab5c494d97819fdc68290e28
Source dataset
uspto-grants-2008_11
Patent number
US07456165B2

Reaction notes

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