Yield: 51%

Reaction Conditions:

Stage #1:5-fluoro-1H-indole-2,3-dione with sodium hydroxide in water at 50; for 0.0833333 h;
Stage #2: with sodium nitrite in water at 0 - 4; for 1 h;
Stage #3: with hydrogenchloride in water for 16 h;

Steps:

4
To a solution of NaOH (1.24 g, 0.031 mol, 1.03 equiv.) in water (19 mL) heated at 50^CC was added 5-Fluoroisatin (5 g, 0.03 mol, 1 equiv.). After 5 minutes, the dark- red solution was cooled to 0°C and a cooled solution of sodium nitrite (2.07 g, 0.03 mol, I equiv.) in water (10 mL) was added slowly, followed by a cooled solution of (95%) (3.12 mL, 0.06 mol , 1.95 equiv.) in water (48 mL). The rate of addition was rapid such that the temperature never rose above 4°C. To reduce the foaming which occurred throughout the period of stirring, a few millilitres of ether were added when necessary. After the end of addition, the cooled solution was stirred for one hour, maintaining the temperature below 4 °C at all times. Then a cooled solution of SnC 1 (16.24 g, 0.072 mol, 2.4 equiv.) in HCl (35%) (24 mL) was added and the mixture was stirred for 16 h. The brown solution was filtrated and the resultion brown solid was washed with water to give a light brown solid (2.73 g, 51%); δ_Η (MeOH-￡/₆) 7.25 (1H, td, J 9.10 Hz and J2.14 Hz, ArH), 7.60 (1H, dd J 9.10 Hz and 4.28 Hz, ArH), 7.74 (1H, dd J 9.10 Hz and 2.10 Hz, ArH); LC-MS-EI 183.1 (MH⁺, 100)

References:

UNIVERSITY COLLEGE LONDON;POSADA, Cristina, Garcia;SELWOOD, David;GARTHWAITE, John;BAKER, David;CLUTTERBUCK, Lisa WO2011/61469, 2011, A1 Location in patent:Page/Page column 34-35