Hydrochloric Acid → 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid

HRID 62416Notes

Reaction equation

[CH3:1][O-:2].[Na+].C[O:5][C:6]([C:8]1[C:9]2[CH:10]=[CH:11][N:12]([CH:18]([CH3:20])[CH3:19])[C:13]=2[CH:14]=[C:15](Br)[CH:16]=1)=[O:7].Cl>CN1C(=O)CCC1.O>[CH:18]([N:12]1[C:13]2[CH:14]=[C:15]([O:2][CH3:1])[CH:16]=[C:8]([C:6]([OH:5])=[O:7])[C:9]=2[CH:10]=[CH:11]1)([CH3:20])[CH3:19]

Participants

Conditions

Temperature: 120 °C

Procedure

Freshly prepared sodium methoxide (500 mg in 5 mL methanol) was added to a stirred suspension of 6-bromo-1-isopropyl-1H-indole-4-carboxylic acid methyl ester (500 mg, 1.68 mmol) and Cul (480 mg, 2.53 mmol) in NMP (8 mL) and then heated at 120° C. for 2 h. The reaction mixture was cooled to room temperature, diluted with water (5 mL) and acidified with 1N HCl. The reaction mixture was filtered through Celite and washed with EtOAc (5 mL). Separated the EtOAc layer from filtrate, dried over anhydrous Na2SO4 and concentrated under reduced pressure to furnish the crude 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid (700 mg), which was used in the next stage without further purification. 1H NMR (400 MHz, DMSO-d6): δ 1.44 (d, J=6.4 Hz, 6H), 3.84 (s, 3H), 4.80-4.76 (m, 1H), 6.87 (d, 1H), 7.33 (t, J=3.2 Hz, 2H), 7.49 (d, J=3.2 Hz, 1H), 12.65 (bs, 1H). LCMS (ES+): m/z=234.11 [M+H].

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationThe reaction mixture was filtered through Celite
washwashed with EtOAc (5 mL)
customSeparated the EtOAc layer from filtrate
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-224e3e2e6c144cfda8c915be966766b8
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09446041B2

Reaction notes

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