3-CHLORO-5-METHOXY-BENZOICACID

White powder

Magnesium turnings (Fluka purum for Grignard reactions) were pre-treated in the following way: The turnings were placed in a glass sintered funnel and 0.1 M of hydrochloric acid was poured onto them. The turnings were stirred with a glass rod for a few seconds and then the acid was washed away with 3 portions of water. Finally, the turnings were washed with 2 portions of acetone and bottled. Tetrahydrofuran (100 mL, 99.95percent) was dried by adding RedAl [(1] g, 70percent wt. in toluene). Pre-treated magnesium turnings (5 g, 200 mmol) were placed in a round bottomed flask, and were flushed with nitrogen 3 times. Dichloroanisole (26 g, 146 mmol) was dissolved in THF (100 mL, [REDAI-DRIED)] and dibromoethane (1.8 g, 10 mmol) was added. The reaction mixture was flushed with nitrogen and then refluxed for 2 hours. Heating was interrupted and dry ice (10 g) was added portionwise over 2 minutes. When all of the dry ice was dissolved, the reaction mixture was poured into ice containing hydrochloric acid (400 mL, 2 M). Extractive work up (ether, 300 mL) gave 11.2 g, 60.2 mmol (yield: [41percent)] of the sub-title compound. [LH-NMR] (500 MHz; [ACETONE-D6)] : A 7.57 (m, [I H), ] 7.49 (m, 1H), 7.23 (m, 1H), 3. 91 (s, 3H)Magnesium turnings (Fluka purum for Grignard reactions) were pre-treated in the following way: The turnings were placed in a glass sintered funnel and 0.1 M of hydrochloric acid was poured onto them. The turnings were stirred with a glass rod for a few seconds and then the acid was washed away with 3 portions of water. Finally, the turnings were washed with 2 portions of acetone and bottled. Tetrahydrofuran (100 mL, 99.95percent) was dried by adding RedAl (1 g, 70percent wt. in toluene). Pre-treated magnesium turnings (5 g, 200 mmol) were placed in a round bottomed flask, and were flushed with nitrogen 3 times. Dichloroanisole (26 g, 146 mmol) was dissolved in THF (100 mL, RedAl-dried) and dibromoethane (1.8 g, 10 mmol) was added. The reaction mixture was flushed with nitrogen and then refluxed for 2 hours. Heating was interrupted and dry ice (10 g) was added portionwise over 2 minutes. When all of the dry ice was dissolved, the reaction mixture was poured into ice containing hydrochloric acid (400 mL, 2 M). Extractive work up (ether, 300 mL) gave 11.2 g, 60.2 mmol (yield: 41percent) of the sub-title compound. [0408] 1H-NMR (500 MHz; acetone-d6): δ7.57 (m, 1H), 7.49 (m, 1H), 7.23 (m, 1H), 3.91 (s, 3H).General procedure: To a stirred solution of 1-(1-hydroxynaphthalen-2-yl)ethan-1-one 6 (2 mmol) in dry DMF (10 ml), benzoic acid derivative(2.2 mmol, commercially available or prepared according to thereported literature procedure), EDCI (3 mmol) and DMAP (3 mmol)were added and the resultant solution stirred for overnight at roomtemperature. After completion of the reaction as indicated by TLC, the reaction mixture was poured into an ice-water solution. Theresulting mixture was extracted with EtOAc. The combined organicextracts were washed with saturated NaCl aqueous, dried overNa2SO4. The solvent was removed under vacuum and the cruderesidue was subjected to silica gel column chromatography to giveintermediate 7.At room temperature, EDCI (527 mg, 2.75 mmol) andDMAP (80 mg, 0.66 mmol) was added to Acetyl chloride (1.9 mL, 28.1 mmol) was added dropwise to a solution of 4 (1.0 g, 5.4 mmol) in MeOH (40 mL) at 0C and the reaction mixture was then stirred at room temperature for 15 h. After evaporation of the organic solvent, the residue was purified by flash column chromatography (silica gel, hexane-methylene chloride 5:1 v/v then switching to hexane-methylene chloride 1:1 v/v) to give compound 5 (0.7 g, 65.1%) as an oil. 1H NMR (300 MHz, CDCl3) delta 3.85 (s, 3H), 3.92 (s, 3H), 7.09 (t, 1H, J = 2.2 Hz), 7.45 (q, 1H, J = 1.3 Hz), 7.61 (t, 1H, J = 1.6 Hz).

Molecular Weight:186.59
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:186.0083718
Monoisotopic Mass:186.0083718
Topological Polar Surface Area:46.5
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes