Sodium Hydroxide → 1-Isopropyl-6-(trifluoromethyl)-1H-indole-4-carbonitrile

HRID 516675Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[CH:15]([CH3:17])[CH3:16].[C:18]([Zn]C#N)#[N:19].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[OH-].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CN(C=O)C>[CH:15]([N:6]1[C:7]2[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=[C:2]([C:18]#[N:19])[C:3]=2[CH:4]=[CH:5]1)([CH3:17])[CH3:16]

Participants

Conditions

Temperature: 120 °C

Procedure

To a 10-mL microwave tube were added 4-bromo-1-(1-methylethyl)-6-(trifluoromethyl)-1H-indole (330 mg, 1.078 mmol), dicyanozinc (146 mg, 1.240 mmol), DMF (4 mL) and water (0.040 mL), and the mixture was degassed for 5 min by bubbling N2. s-Phos (48.7 mg, 0.119 mmol) and tris(dibenzylideneacetone)dipalladium(0) (49.4 mg, 0.054 mmol) were added. The tube was sealed and the mixture was heated at 120° C. for 2.5 h. 1 N NaOH (3 mL) was added and the mixture was extracted with EtOAc (3x). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 70% EtOAc/hexanes) to give the title compound (210 mg, 77%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.61 (m, 6H), 4.79 (spt, J=6.69 Hz, 1H), 6.84 (d, J=3.28 Hz, 1H), 7.59 (d, J=3.28 Hz, 1H), 7.73 (s, 1H), 7.88 (s, 1H). MS: (M+H)+=253.2.

Workup

customthe mixture was degassed for 5 min
customby bubbling N2
customThe tube was sealed
extractionthe mixture was extracted with EtOAc (3x)
dry with materialThe extract was dried over Na2SO4
concentrationconcentrated
customThe residue was purified

Sources & evidence

ORD record: ord-e60d74f527ab4403bb227d007df93bf1
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09114141B2

Reaction notes

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