1,5-Dibromopentane → HCID 16050356, compound

Temperature

25 °C

7-Fluoro-1,3-dihydro-indol-2-one (EXAMPLE 99, step 4) (1.16 g, 7.68 mmol) and lithium chloride (0.81 g, 19.2 mmol) were dissolved in tetrahydrofuran (50 mL) and cooled to 0° C. n-Butyllithium (6.14 mL, 15.4 mmol) was added dropwise and the mixture was stirred 15 minutes. 1,5-Dibromopentane (1.05 mL, 7.7 mmol) was added slowly and stirring was continued for 2 hours at o° C. then warmed to 25° C. After 16 hours the reaction was quenched with a saturated aqueous solution of ammonium chloride. The mixture was diluted with ether, washed with water, and saturated brine. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Isco chromatography (Redisep, silica, gradient 5% to 40% ethyl acetate in hexane) to afford 0.90 g (54%) of 7′-fluorospiro-[cyclohexane-1,3′-indol]-2′(1′H)-one. HPLC purity 95.9% at 210-370 nm, 19.2 min.; Xterra MSC18, 5u, 150×3.0 mm column, 0.5 mL/minutes, 95/5-5/95 (0.1% formic acid in H2O/MeOH) for 20 minutes, hold 3 min.

1. additionwas added dropwise
2. stirringstirring
3. waitwas continued for 2 hours at o° C
4. customAfter 16 hours the reaction was quenched with a saturated aqueous solution of ammonium chloride
5. additionThe mixture was diluted with ether
6. washwashed with water, and saturated brine
7. customThe organic layer was separated
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude product was purified via Isco chromatography (Redisep, silica, gradient 5% to 40% ethyl acetate in hexane)

ORD record

ord-e41b9b9173444ed1b72d2905ef42b6c1

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07517899B2