4-CHLORO-1-BENZOTHIOPHENE-2-CARBOXYLIC ACID

Preparation 201 4-chlorobenzo[b]thiophene-2-carboxylicStir a mixture of methyl 4-chlorobenzo[b]thiophene-2-carboxylate (1.0 g, 4.44 mmol) and LiOH-HPreparation 201 4-chlorobenzo[b]thiophene-2-carboxylicStir a mixture of methyl 4-chlorobenzo[b]thiophene-2-carboxylate (1.0 g, 4.44 mmol) and LiOH-HPreparation 201 4-chlorobenzo[b]thiophene-2-carboxylicStir a mixture of methyl 4-chlorobenzo[b]thiophene-2-carboxylate (1.0 g, 4.44 mmol) and LiOH-HMethyl 4-chlorobenzo[b]thiophene-2-carboxylate (600 mg, 2.7 mmol), LiOH (318 mg, 13.3 mmol), THF (6 mL) and water (8 mL) were added to a 50 mL round bottom flask, and stirred at room temperature until starting material was consumed. The majority of THF was removed in vacuo, The resulting crude mixture was acidified with aqueous HCI (‘—pH = 3) and cooled in an ice bath. The solids were filtered and washed with cold water (about 6 ml) to give title compound (523 mg, 91percent).Sodium 4-chlorobenzo[b] thiophen-2-carboxylate (2.40 g) was dissolved in water (33 ml) at 60°C. Concentrated hydrochloric acid (1.3 ml) was added to the solution at the same temperature, and the resulting mixture was stirred. The precipitated crystals were collected by filtration, washed with water, and then dried to obtain 2-carboxy-4-chlorobenzo[b] thiophene. Yield: 1.61 g ^- MR (DMS0-dIn 1L reaction flask was added 95g of water, dissolved in 62.5g of potassium hydroxide was stirred, cooled to room temperature dropping 40g mercaptoacetic acid, and then followed by addition of 50g2.6-dichlorobenzaldehyde, 250g xylene and 2gTBAB, Heated to reflux with vigorous stirring, and the reaction was maintained for 3 hours, cooled to 85 ° C to join 400g of water to dissolve the solid, poured into a separatory funnel at 85 ° C static stratification, The water layer was moved to the reaction flask, hydrochloric acid was added dropwise hot until pH <2, stirred for half an hour and filtered, the filter cake rinsed with hot water to dry, oven dried to obtain 42g 4-chloro-1-benzothiophen-2 -carboxylic acid.A suspension of (Z)-3-(2, 6-dichlorophenyl-2-mercapto-2- propenoic acid (72.4 g) and water (362 ml) was stirred at room temperature. Further, potassium hydroxide (40.8 g) was added, and the mixture was heated under reflux for 4 hours . After the mixture was allowed to cool, the mixture was stirred for 1 hour while cooling with ice. The precipitated crystals ((Z)-3-(2, 6- dichlorophenyl-2-mercapto-2-propenoic acid potassium salt) were collected by filtration and washed with cold water. After the crystals were suspended in water, 35percent concentrated hydrochloric acid (32 ml) was added (pH = 1), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration and dried to obtain 2-carboxy-4- chlorobenzo[b] thiophene. Yield of 48.8 g ^- MRiDMSO-de) 6ppm; 7.53 (1H, t, J = 7.7 Hz), 7.58 (1H, dd, J = 7.7, 1.3 Hz), 8.03 (1H, d, J = 0.5 Hz), 8.07 (1H, d, J = 7.6 Hz).After potassium hydroxide (30.8 g) was dissolved in water (179 ml), thioglycolic acid (19.4 g) was added to the solution, and 2 , 6-dichlorobenzaldehyde (32.0 g) was further added. The resulting mixture was heated under reflux for 2.5 hours. The mixture was allowed to cool, and then allowed to stand at room temperature overnight. The precipitated crystals (potassium 4- chlorobenzo[b] thiophen-2-carboxylate) was collected by filtration and washed with cold water. Further, the crystals were dispersed in water (256 ml). After concentrated hydrochloric acid (20 ml) was added thereto, the resulting mixture was stirred for 1 hour. The precipitated crystals were collected by filtration and washed with water. Crude crystals of this 2-carboxy-4- chlorobenzo[b] thiophene were dispersed in ethyl acetate (96 ml), and washed at room temperature. The precipitated crystals were washed with ethyl acetate, and then dried to yield 29.12 g of a dried product. The dried product was further washed with ethyl acetate, and the wash was concentrated to 70 ml. The precipitated secondary crystals were collected and dried to obtain 2-carboxy- 4-chlorobenzo[b]thiophene (1.35 g) . Yield: 30.5 g White crystals ^-NMRiDMSO-de) δρρπΐ; 7.53 (1H, t, J= 7.7 Hz), 7.58 (1H, dd, J= 7.7. 1.3 Hz), 8.03 (1H, d, J= 0.5 Hz), 8.07 (1H, d, J= 7.6 Hz).

Molecular Weight:212.65
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:211.9698783
Monoisotopic Mass:211.9698783
Topological Polar Surface Area:65.5
Heavy Atom Count:13
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes