Cesium carbonate → 5-Nitroindole

HRID 1964392Notes

Reaction equation

HRID 1964392 reaction equation
CC1C=CC(S(OC[C@@H]2COC(C)(C)O2)(=O)=O)=CC=1.C([C:24]1[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29]([N+:33]([O-:35])=[O:34])=[CH:28][CH:27]=2)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[N+:33]([C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][CH:28]=1)[NH:25][CH:24]=[CH:32]2)([O-:35])=[O:34]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 2723760(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-Toluenesulfonate2×HCID 105849132-(tert-Butyl)-5-nitro-1H-indole

Product 1

HCID 225235-NitroindoleYield 134.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) in anhydrous DMF (10 mL) under nitrogen gas was added 2-tert-butyl-5-nitro-1H-indole (1.00 g, 4.58 mmol) followed by Cs2CO3 (2.99 g, 9.16 mol). The mixture was stirred and heated at 80° C. under nitrogen gas. After 20 hours, 50% conversion was observed by LCMS. The reaction mixture was re-treated with Cs2CO3 (2.99 g, 9.16 mol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) and heated at 80° C. for 24 hours. The reaction mixture was cooled to room temperature. The solids were filtered and washed with ethyl acetate and hexane (1:1). The layers were separated and the organic layer was washed with water (2×10 mL) and brine (2×10 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane/hexane=1.5/1) to give (R)-2-tert-butyl-1-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-nitro-1H-indole (1.0 g, 66%). 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J=2.2 Hz, 1H), 8.08 (dd, J=2.2, 9.1 Hz, 1H), 7.49 (d, J=9.1 Hz, 1H), 6.00 (s, 1H), 4.52-4.45 (m, 3H), 4.12 (dd, J=6.0, 8.6 Hz, 1H), 3.78 (dd, J=6.0, 8.6 Hz, 1H), 1.53 (s, 3H), 1.51 (s, 9H), 1.33 (s, 3H).

Workup

  1. temperatureheated at 80° C. for 24 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationThe solids were filtered
  4. washwashed with ethyl acetate and hexane (1:1)
  5. customThe layers were separated
  6. washthe organic layer was washed with water (2×10 mL) and brine (2×10 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel (dichloromethane/hexane=1.5/1)

Sources & evidence

ORD record
ord-53b9c9354baf4cb2b920a6b56d38c350
Source dataset
uspto-grants-2013_04
Patent number
US08415387B2

Reaction notes

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