Methyl iodide → 2-Methyl-5-[(phenylmethyl)oxy]-1-(phenylsulfonyl)-1H-indole

HRID 1188525Notes

Reaction equation

[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH:13]=[CH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li][CH2:28]CCC.CI>C1COCC1>[CH3:28][C:13]1[N:14]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:15]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[CH:17][CH:16]=2

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 5-[(phenylmethyl)oxy]-1-(phenylsulfonyl)-1H-indole (1.6 g, 4.4 mmol, synthesized as described in Example 22A) in THF (10 mL), under N2, at −78° C., was added n-BuLi (2.5 M solution in hexanes, 2.15 mL, 5.37 mmol) dropwise. After stirring at −78° C. for 30 min, methyl iodide (0.94 g, 6.6 mmol) was added. After 30 min, the −78° C. bath was removed. The solution was warmed to rt. 5% HCl (10 mL) was then added and the mixture was partitioned between EtOAc and water. The organic phase was washed with water and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (20-70% EtOAc-hexanes gradient) to afford the title compound (0.8 g, 77% yield): MS (ES) m/z 478 (M+1).

Workup

waitAfter 30 min
customthe −78° C. bath was removed
temperatureThe solution was warmed to rt
addition5% HCl (10 mL) was then added
customthe mixture was partitioned between EtOAc and water
washThe organic phase was washed with water
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography (20-70% EtOAc-hexanes gradient)

Sources & evidence

ORD record: ord-d17b048417b1422fa9809627e218a526
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673948B2

Reaction notes

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