Hydrochloric Acid → HCID 69320268, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of (R)-3,4-dihydro-8-isopropoxy-3-methyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline (13 mg, 0.04 mimol) and K2CO3 (28 mg, 0.2 mmol, 5 eq) in 1 ml DMF (0.04 M) was added allylbromide (0.03 mL, 0.4 mmol, 10 eq). The reaction was heated to 50° C. and allowed to stir for 12 h, whereupon the reaction was poured into 10 mL water and neutralized with 1N HCl. The aqueous layer was extracted with EtOAc (2 ×40 mL/mmol) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, concentrated to afford 10 mg (75%) of (R)-4-allyl-3,4-dihydro-8-isopropoxy-3-methyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline. This material (10 mg, 0.03 mmol) was carried on directly according to General Method 4 (EXAMPLE 1) by treatment with 2 mL concentrated HCl (001.M) and heated at 50° C. for 6 h to afford 6 mg (67%) of Compound 106 after silica gel column chromatography (gradient 3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution) 1H NMR (500 MHz, CDCl3) δ 11.89 (bs, 1H), 7.11 (s, 1H), 7.00 (d, J=8.8, 1H), 6.93 (d, J=8.8, 1H), 5.86 (m, 1H), 5.24 (m, 2H), 4.10 (m, 2H), 3.90 (m, 2H), 3.55 (m, 1H), 1.22 (d, J=6.8, 3H).

Provenance & Evidence