Dimethylformamide → 3-Ethyl-5-trifluoromethyl-indol-1-ylamine

HRID 2382056Notes

Reaction equation

[H-].[Na+].[CH2:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([F:17])([F:16])[F:15])[CH:12]=2)[NH:7][CH:6]=1)[CH3:4].C[N:19](C=O)C>>[CH2:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([F:17])([F:15])[F:16])[CH:12]=2)[N:7]([NH2:19])[CH:6]=1)[CH3:4]

Participants

Reactant 3

HCID 6228Dimethylformamide

HCID 24758Sodium hydride

HCID 597262573-ethyl-5-trifluoromethyl-1H-indole

Product 1

HCID 685542413-Ethyl-5-trifluoromethyl-indol-1-ylamineYield 50%

Conditions

Temperature: 0 °C

Procedure

A suspension of NaH (7 g, 176 mmol, 60% in mineral oil) in DMF (50 mL) at 0° C. is treated with 3-ethyl-5-trifluoromethyl-1H-indole (2.4 g, 11.3 mmol) and stirred at 0° C. for 1 h. The mixture is treated with HOSA (6.6 g, 59 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice, filtered through a pad of Celite, and extracted with EtOAc (3×150 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-50% EtOAc in heptane to afford 3-ethyl-5-trifluoromethyl-indol-1-ylamine (1.3 g, 50%). MS: 229 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.84 (s, 1H), 7.45 (s, 2H), 7.02 (s, 1H), 4.74 (s, NH2, 2H), 2.77 (q, 2H), 1.31 (t, 3H).

Workup

additionThe mixture is treated with HOSA (6.6 g, 59 mmol) portion wise
temperaturewarmed to rt over 2 h
additionThe mixture is then poured over ice
filtrationfiltered through a pad of Celite
extractionextracted with EtOAc (3×150 mL)
dry with materialThe combined organic layer is dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue is purified by silica gel chromatography
washeluting with 10%-50% EtOAc in heptane

Sources & evidence

ORD record: ord-afaef8eba2934d19b3cfee9bf482375d
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258130B2

Reaction notes

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