Hydroxyamine hydrochloride → tert-butyl 5-(1-aminoethyl)-4-chloro-1H-indole-1-carboxylate

HRID 475308Notes

Reaction equation

C(=[N:14][CH:15]([C:17]1[C:18]([Cl:33])=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:21]=[CH:20]2)[CH3:16])(C1C=CC=CC=1)C1C=CC=CC=1.Cl.NO>CO>[NH2:14][CH:15]([C:17]1[C:18]([Cl:33])=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:21]=[CH:20]2)[CH3:16]

Participants

Conditions

Temperature: 40 °C

Procedure

To a stirred solution of 324 (880.0 mg, 1.92 mmol) in anhydrous MeOH (20 mL) was added hydroxylamine hydrochloride (532.9 mg, 7.70 mmol), and the reaction mixture was stirred at 40° C. under N2 for 16 h. Volatile solvents were removed in vacuo, and the residue was diluted with EtOAc. The organic layer was washed with sat'd. aq. NaHCO3, water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/heptane gradient (20 to 100% EtOAc), followed a MeOH/EtOAc (+1% TEA) gradient (0 to 80% MeOH) to afford 290 mg (51.3%) of tert-butyl 5-(1-aminoethyl)-4-chloro-1H-indole-1-carboxylate (326) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.99 (d, J=8.7 Hz, 1H), 7.73 (d, J=3.7 Hz, 1H), 7.64 (d, J=8.7 Hz, 1H), 6.71 (d, J=3.7 Hz, 1H), 4.49 (d, J=6.6 Hz, 1H), 2.36-1.90 (m, 2H), 1.63 (s, 9H), 1.26 (d, J=6.6 Hz, 3H).

Workup

customVolatile solvents were removed in vacuo
additionthe residue was diluted with EtOAc
washThe organic layer was washed with sat'd
dry with materialaq. NaHCO3, water and brine, dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by SiO2 chromatography
washeluting with an EtOAc/heptane gradient (20 to 100% EtOAc)

Sources & evidence

ORD record: ord-10e38649ab7d4f74a43cade0285c3a1f
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

Loading…