Potassium bis(trimethylsilyl)amide → Methyl 3-bromo-4-{(2rs)-2-[(5-chloro-1-methyl-1h-indol-2-yl)carbonyl]heptyl}benzoate

HRID 1818619Notes

Reaction equation

HRID 1818619 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11](=[O:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:5]2.[CH3:19][Si]([N-][Si](C)(C)C)(C)C.[K+].[Br:29][C:30]1[CH:31]=[C:32]([CH:37]=[CH:38][C:39]=1[CH2:40]Br)[C:33]([O:35][CH3:36])=[O:34]>C1COCC1>[Br:29][C:30]1[CH:31]=[C:32]([CH:37]=[CH:38][C:39]=1[CH2:40][CH:12]([C:11]([C:6]1[N:7]([CH3:19])[C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=2)=[O:18])[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:33]([O:35][CH3:36])=[O:34]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 10804694Methyl 3-bromo-4-(bromomethyl)benzoateHCID 66777278HCID 66777278, compound

Product 1

HCID 67482316Methyl 3-bromo-4-{(2rs)-2-[(5-chloro-1-methyl-1h-indol-2-yl)carbonyl]heptyl}benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−78° C.) solution of the title compound of Example 1 Step B (161 mg, 0.58 mmol) in THF (3 mL) was added KHMDS (2.30 mL, 0.5 M in toluene, 1.15 mmol). After 30 min, a solution of the title compound of Example 2 Step A (357.0 mg, 1.16 mmol) in THF (3 mL) was added, and the resultant mixture was allowed to warm slowly to room temperature over 15 h. The mixture was then quenched by addition of sat. aq. NaHCO3, and the aqueous phase was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was taken forward without further purification. A small portion was removed and purified by reverse phase HPLC (85 to 100% CH3CN in H2O, both with 0.1% v/v TFA) for characterization: LCMS C, tr=3.12 min, m/z 506.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J=1.5 Hz, 1H), 7.79 (dd, J=8.0, 2.0 Hz, 1H), 7.63 (d, J=1.5 Hz, 1H), 7.33-7.25 (m, 3H), 7.11 (s, 1H), 4.02 (s, 3H), 3.89 (s, 3H), 3.83 (dddd, J=9.0, 9.0, 6.0, 6.0 Hz, 1H), 3.21 (dd, J=13.5, 9.0 Hz, 1H), 3.06 (dd, J=13.5, 6.0 Hz, 1H), 1.91-1.83 (m, 2H), 1.63-1.56 (m, 1H), 1.39-1.26 (m, 5H), 0.86 (t, J=6.5 Hz, 3H).

Workup

  1. customThe mixture was then quenched by addition of sat. aq. NaHCO3
  2. extractionthe aqueous phase was extracted with EtOAc
  3. dry with materialThe organic phase was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was taken forward without further purification
  6. customA small portion was removed
  7. custompurified by reverse phase HPLC (85 to 100% CH3CN in H2O
  8. customLCMS C, tr=3.12 min, m/z 506.2 [M+H]+

Sources & evidence

ORD record
ord-15cecf10aff047e2be1b4e6edaa02447
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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