4,5,6,7-Tetrahydrobenzo[b]thiophene-2-carboxylic acid

(1) 1.0 g of 4, 5, 6, 7-Tetrahydro-benzo[b]thiophene-2-carbonyl Chloride (8); 4, 5, 6, 7-Tetrahydro-benzo[b]thiophene-2-carboxylic acid (1.0 g, 5.50 mmol) is dissolved in dichloromethane [DCM] (25 mL) that contains 5 drops of N, N-dimethylformamide [DMF] under nitrogen and cooled to 0 C. Oxalyl chloride (13.7 mL of a 2.0M solution in DCM) is added via syringe and allowed to warm to RT over 1 hour. All solvent is then removed under reduced pressure, and the resultant oil is reduced from toluene (3×20 mL) to remove residual oxalyl chloride. The residue is then dissolved in ethyl acetate and washed with saturated sodium bicarbonate (1×100 mL), then washed with saturated sodium chloride (1×100 mL) and dried over sodium sulfate. The solution is then filtered and concentrated under reduced pressure to give 4, 5, 6, 7-tetrahydro-benzo[b]thiophene-2-carbonyl chloride (8) as an off-white solid (1.03 g).A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen, charged with A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen, charged with A 5 L 3-neck round bottom flask(RBF) equipped with an overhead stirrer, temperature probe and a 1 L droppingfunnel was charged sequentially with 300g (1.65 mol) of compound I(4, 5, 6, 7-tetrahydrobenzo[b]thiophene-2-carboxylicacid), 1.4 L of dichloromethane(DCM) and 2 mL (cat.) of dimethylformamide (DMF). Oxalyl chloride (900 mL, 1.8 mol) in thedropping funnel was added drop-wise to the suspension of acid in about 3 h. The reaction temperature decreased from 17 oCto 14 oC during the addition with a slow gas evolution. After the reaction mixture was stirred at 25C overnight, the resulting light yellow solution was concentrated under vacuum. The reaction mixture was added with toluene(1 L) and evaporated under vacuum to give a thick oil which may solidify.General procedure: To a mixture of 4-(tert-butyl)benzoic acid (1 g, 5.61 mmol) in DCM (30 mL) was added oxalyl chloride (0.57 mL, 6.74 mmol) and DMF (0.05 mL) at 0 C. The reaction mixture was stirred at room temperature for 4 h. The resulting mixture was then concentrated to afford the crude 4-(tert-butyl)benzoyl chloride. And then to a mixture of 3-bromo-2-methylaniline (1.11 g, 6 mmol) in dry DCM (50 mL) was slowly added crude 4-(tert-butyl)benzoyl chloride and DIPEA (1 mL, 5 mmol) at 0 C. The resulting mixture was stirred for 10 min at room temperature, and then quenched by MeOH (5 mL), concentrated and purified by flash column chromatography (0-2%MeOH in DCM) to afford S1a (1.86 g, two steps yield 96%) as a white solid.4, 5, 6, 7-Tetrahydro-benzo[b]thiophene-2-carboxylic acid (1.Og, 5.50 mmol) is dissolved in dichloromethane [DCM] (25 mL) that contains 5 drops of N, N- dimethylformamide [DMF] under nitrogen and cooled to O0C. Oxalyl chloride (13.7 mL of a 2.0M solution in DCM) is added via syringe and allowed to warm to RT over 1 hour. All solvent is then removed under reduced pressure, and the resultant oil is

Molecular Weight:182.24
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:182.04015073
Monoisotopic Mass:182.04015073
Topological Polar Surface Area:65.5
Heavy Atom Count:12
Complexity:193
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes