Water → 2-(1-Tert-butoxycarbonylindol-3-yl)propionitrile

HRID 552219Notes

Reaction equation

HRID 552219 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]#[N:19])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][Si]([N-][Si](C)(C)C)(C)C.[Na+].IC.O>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH:17]([C:18]#[N:19])[CH3:20])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 15378323tert-Butyl 3-(cyanomethyl)-1H-indole-1-carboxylate

Product 1

HCID 252230692-(1-Tert-butoxycarbonylindol-3-yl)propionitrileYield 79.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of 3-cyanomethyl-indole-1-carboxylic acid tert-butyl ester (2.15 g, 8.39 mmol) in THF (40 ml) was cooled to −78° C. under an argon atmosphere. Sodium bis(trimethylsilyl)amide (1 M in THF, 10 ml, 10 mmol) was added thereto and the cold solution was stirred for 30 minutes. Iodomethane (627 uL, 10 mmol) was added thereto and the reaction mixture was stirred 1.5 hr while gradually warming to 0° C. H2O (100 ml) was added thereto and the solution was brought to RT and diluted with EtOAc (250 ml). The aqueous layer was removed and extracted with EtOAc (250 ml). The combined organic layers were washed with aqueous HCl (1N, 3×50 ml), followed by brine, then dried over MgSO4, filtered, and concentrated to an orange oil. Purification via column chromatography (hexanes:ethyl acetate) gave 3-(cyano-methyl-methyl)-indole-1-carboxylic acid tert-butyl ester (1.8 g). 1H-NMR (300 MHz, DMSO-d6): δ 8.09 (d, 1); 7.73 (d, 1); 7.69 (s, 1); 7.74-7.29 (m, 2); 4.56 (q, 1); 1.66 (d, J=7.2, 3); 1.63 (s, 9).

Workup

  1. stirringthe reaction mixture was stirred 1.5 hr
  2. customwas brought to RT
  3. customThe aqueous layer was removed
  4. extractionextracted with EtOAc (250 ml)
  5. washThe combined organic layers were washed with aqueous HCl (1N, 3×50 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to an orange oil
  9. customPurification via column chromatography (hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-2ccce098085f45e8b60fe185b74c415c
Source dataset
uspto-grants-2011_05
Patent number
US07951801B2

Reaction notes

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