Iodine → HCID 23353962, compound

Over a period of 1 h a solution of cyclobutyl bromide (13 g, 0.1 mol) in diethyl ether (150 ml) was added dropwise to a slurry of magnesium turnings (2.5 g, 0.11 mol) and a crystal of iodine in diethyl ether (20 ml) at reflux. The mixture was stirred for a further hour whereupon the Grignard solution was cannulated into a pressure equalising dropping funnel, attached to a three-necked round-bottomed flask, which was under an atmosphere of nitrogen. A solution of 2-aminobenzonitrile (3.78 g, 32 mmol) at 0° C. in diethyl ether (50 ml) was treated dropwise with the Grignard reagent prepared above, over a period of 15 min. Once the addition was complete, the mixture was warmed to room temperature and stirred for 16 h under nitrogen. The solution was cooled to 0° C., quenched with 5N hydrochloric acid (20 ml), and basified using solid sodium hydroxide (4 g). The aqueous solution was extracted with ethyl acetate (2×100 ml) and the combined organic layers were dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel using 2:1 petrol:ethyl acetate as the eluant. This gave a yellow oil which was then azeotroped with toluene (2×80 ml) to-give the title compound (4 g, 71%) as a pale yellow solid. mp 55° C. 1H NMR (250 MHz, CDCl3) 5 1.72-2.48 (6H, m), 3.80-4.00 (1H, m), 6.23 (2H, brs), 6.50-6.61 (2H, m), 7.11-7.22 (1H, m), 7.45-7.54 (1H, m).

1. customattached to a three-necked round-bottomed flask
2. customprepared above, over a period of 15 min
3. additionOnce the addition
4. stirringstirred for 16 h under nitrogen
5. temperatureThe solution was cooled to 0° C.
6. customquenched with 5N hydrochloric acid (20 ml)
7. extractionThe aqueous solution was extracted with ethyl acetate (2×100 ml)
8. dry with materialthe combined organic layers were dried (Na2SO4)
9. customevaporated
10. customThe residue was chromatographed on silica gel using 2:1 petrol
11. customThis gave a yellow oil which
12. customwas then azeotroped with toluene (2×80 ml)

ORD record

ord-8e8b0cd73dc249de89efc92ef382b107

Source dataset

uspto-grants-1994_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05360802