Trichloroacetonitrile → (+/-)-1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethyl 2,2,2-trichloroacetimidate

HRID 913970Notes

Reaction equation

HRID 913970 reaction equation
C1CCN2C(=NCCC2)CC1.[Cl:12][C:13]1[CH:14]=[C:15]2[C:19](=[C:20]([CH:22]([OH:24])[CH3:23])[CH:21]=1)[N:18]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:17]=[C:16]2[C:33]#[N:34].[Cl:35][C:36]([Cl:40])([Cl:39])[C:37]#[N:38]>C1COCC1>[Cl:35][C:36]([Cl:40])([Cl:39])[C:37](=[NH:38])[O:24][CH:22]([C:20]1[CH:21]=[C:13]([Cl:12])[CH:14]=[C:15]2[C:19]=1[N:18]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[CH:17]=[C:16]2[C:33]#[N:34])[CH3:23]

Participants

5

Reactant 3

HCID 11011TrichloroacetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57546168(+/-)-5-chloro-7-(1-hydroxyethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile

Product 1

HCID 57546157(+/-)-1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethyl 2,2,2-trichloroacetimidateYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DBU (0.020 mL, 0.130 mmol) was added to a solution of (±)-5-chloro-7-(1-hydroxyethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (456 mg, 1.299 mmol) and Trichloroacetonitrile (0.391 mL, 3.90 mmol) in THF (10 mL) and the reaction was stirred for one hour. The solvent was evaporated and the reaction was purified by chromatography on SiO2 with 10:89:1 ethyl acetate/hexanes/triethylamine to give (±)-1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethyl 2,2,2-trichloroacetimidate (472 mg, 0.953 mmol, 73.3% yield) as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 8.22 (s, 1H), 7.66 (d, J=2.0 Hz, 1H), 7.61 (s, 1H), 7.52 (d, J=2.0 Hz, 1H), 6.60 (q, J=6.3 Hz, 1H), 6.27 (d, J=11.3 Hz, 1H), 5.25 (d, J=11.3 Hz, 1H), 3.48 (m, 2H), 1.72 (d, J=6.3 Hz, 3H), 0.80-1.05 (m, 2H), −0.02 (s, 9H).

Workup

  1. customThe solvent was evaporated
  2. customthe reaction was purified by chromatography on SiO2 with 10:89:1 ethyl acetate/hexanes/triethylamine

Sources & evidence

ORD record
ord-73902588d6f84f9086206146ac4e5f60
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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