4-(1-AMINO-ETHYL)-BENZOICACIDMETHYLESTER

Methyl 4-acetylbenzoate (1.07 g, 6 mmol), methylamine (33 percent in EtOH, 4.5 mL), methylamine hydrochloride (1.62 g, 24.0 mmol) and sodium cyanoborohydride (0.56 g, 9.0 mmol) were dissolved in a mixture of THF (12 mL) and Methanol (7 mL) and the reaction stirred at 65 General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL, 2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq), were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL), respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1, 4]oxazine product.General procedure: To a stirred solution ofthe corresponding amine (2 mmol) in anhydrous CH2Cl2 containing drytriethylamine (5 mmol) a solution of 3 or 15a-c (2.5 mmol) in anhydrousCH2Cl2 (5 mL) was added dropwise over 15 min at 0 C. Afterstirred for another 5 h at room temperature, water was added, and themixture was extracted with CH2Cl2. The combined organic phase wasdried (Na2SO4) and filtered to obtain the crude products, which werepurified by column chromatography using silica gel and a CH2Cl2/MeOH mixture. (CH2Cl2: MeOH=100:1)To a solution of methyl 4-(1-(hydroxyimino)ethyl)benzoate (800 mg, 4.14 mmol) in methanol (30 mL) was added Raney-Nickel (700 mg). The reaction mixture was stirred under hydrogen (50 psi) at rt for 4 hrs. On completion, the mixture was filtered. The filtrate was concentrated in vacuo to give the title compound. 'H NMR (4001V11{z, DMS 0-cl6) = 7.90 (d, J = 8.4 Hz, 2H), 7.52 (d, J= 8.0 Hz, 2H), 4.06 (q, J= 6.8 Hz, 1H), 3.84 (s, 3H), 1.25 (d, J 6.8 Hz, 3H).

Molecular Weight:179.22
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:179.094628657
Monoisotopic Mass:179.094628657
Topological Polar Surface Area:52.3
Heavy Atom Count:13
Complexity:174
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes