Benzoic acid, 4-amino-3-(1-methylethoxy)-, methyl ester (9CI)

3-Isopropoxy-4-aminomethylbenzoate 4-Amino-3-isopropoxy-benzoic acid methyl ester (3-4). To a solution of 2.045 g (12.23 mmol) methyl 4-amino-3-hydroxybenzoate (3-3) in 40 ml acetone, 1.83 ml 2-iodopropane (18.34 mmol, 1.5 eq.) and 7.97g (24.45 mmol, 2.0 eq.) CsMethyl3-hydroxy-4-aminobenzoate (ABCR: 100 mg, 0.60 mmol) caesium carbonate (396 mg, 1.22 mmol) were taken up in acetone (4 mL) and 2-iodopropane (90 μl, 0.90 mmol) added and reaction heated in microwave (CEM discover; 150 W) to 120° C. and held for 30 mins A further aliquot of 2-iodopropane (90 μl, 0.90 mmol) was added and reaction heated again to 120° C. in microwave, holding for a further 30 minsThe reaction was repeated twice on a 0.89 mmol scaleReaction mixtures were combined and evaporated to dryness and the residue partitioned between, ethyl acetate (40 ml) and water (50 ml). The organic phase was separated and the aqueous re-extracted with ethyl acetate (40 ml). Combined organic extracts were washed with brine, dried over magnesium sulphate and evaporated to give a brown oil which was purified by column chromatography, on silica (40 g cartridge; ISCO companion) eluting with a rising gradient of 5-50percent ethyl acetate in iso-hexane. Product containing fractions were combined and evaporated to dryness to afford the product as a yellow oil (301 mg, 60percent)1H NMR (400.132 MHz, DMSO-D6) δ 1.28 (d, 6H), 3.75 (s, 3H), 4.53 (m, 1H), 5.51 (s, 2H), 6.66 (d, 1H), 7.31 (m, 1H), 7.37 (m, 1H); MS m/z 209.4 [M+H]+.This compound was prepared with minor modifications as described in PCT int. Appl. 2005079541 (01 Sept. 2005) as follows: To a solution of Methyl 4-amino-3 -hydro ybenzoate (l .Og, 6.0 mmol) in acetone (20 mL) at ambient temperature was added 2-bromopropane (l .lg, 9.0 mmol) followed by cesium carbonate (3.9g, 12 mmol) each in one portion. The resulting mixture was heated a reflux temperature for 6 hr. Concentrated ammonium hydroxide (5 mL) was added and the mixture was refluxed for an additional 30 min. After cooling to ambient temperature the mixture was diluted with water (100 mL) and extracted with 3X 75 mL of diethyl ether. The combined extracts were washed with 2X 50 mL of brine and dried over magnesium sulfate. The mixture was filtered and concentrated in vacuo. The residue was taken up in diethyl ether, silica gel was added and the mixture concentrated in vacuo. The residue was transferred to a pre- column and purified by chromatography using initially hexanes (1 min.) as eluent. The eluent was modified to 30percent ethyl acetate/hexanes over a 15 min. period and kept at 30percent ethyl acetate/hexanes for the remainder of the purification. Fractions containing the pure desired component were combined and concentrated in vacuo to give 1.03g (82.7percent yield) of a pale yellow oil that solidified on standing to a white solid. MS: m/z 210.1 (MKT). 1H NMR (500 MHz, DMSO-d

Molecular Weight:209.24
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:209.10519334
Monoisotopic Mass:209.10519334
Topological Polar Surface Area:61.6
Heavy Atom Count:15
Complexity:218
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes