Diethyl Ether → 5-Fluoro-2-methyl-indol-1-ylamine

HRID 2381890Notes

Reaction equation

CC(C)([O-])C.[K+].[F:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([CH3:17])=[CH:11]2.Cl[NH2:19].CCOCC>CN(C=O)C>[F:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([NH2:19])[C:12]([CH3:17])=[CH:11]2

Participants

Conditions

Temperature: 23 °C

Procedure

A solution of potassium tert-butoxide (1.84 g, 16.43 mmol) and 5-fluoro-2-methylindole (1.21 g, 8.09 mmol) in DMF (20 mL) is stirred under N2 at rt for 60 min. A solution of monochloroamine in ether (65 mL, 9.75 mmol) is added via an addition funnel over 10 min. The resulting mixture is stirred at 23° C. for 2 hours, and then concentrated in vacuo. The residue is partitioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10% EtOAc in heptane to afford 5-fluoro-2-methyl-indol-1-ylamine (290 mg, 22%) as a solid. MS: 165 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.24-7.19 (m, 1H), 7.12 (dd, 1H), 6.92 (dt, 1H), 6.12 (s, 1H), 4.23 (br s, 2 H), 2.39 (s, 3H).

Workup

concentrationconcentrated in vacuo
customThe residue is partitioned between EtOAc and water
customThe organic phase is separated
washwashed with saturated aqueous NaHCO3, water and brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue is purified by silica gel chromatography
washeluting with 10% EtOAc in heptane

Sources & evidence

ORD record: ord-88939352958f4025a91624f2c324f927
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258130B2

Reaction notes

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