1914-02-9, A common heterocyclic compound, 1914-02-9, name is 3,3-Dimethylindoline, molecular formula is C10H13N, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a solution of 3- (chlorosulfonyl) benzoic acid (456 mg, 2.07 mmol, Aldrich) in CH2Cl2 (15 [ML)] was added DMF (15 [UL)] followed by oxalyl chloride (270 [; J, L,] 3.10 mmol). After stirring for 1.5 hours, the solvent and excess oxalyl chloride were removed by rotary evaporation. The residue was dissolved in toluene (15 mL), and [METHYL 2-AMINO-5-CYANOBENZOATE (370 MG,] 2.10 mmol) was added. The mixture was heated in a [105 C] oil bath for 2 hours, and the toluene was then removed by rotary evaporation. The residue was dissolved in [CH2CLZ] (6 mL), and a mixture of 3,3- [DIMETHYLINDOLINE,] descrinbed by Kucerovy et al. in Synth. Commun. 1992, 22 (5), 729- 733, (342 mg, 2.32 mmol) and triethylamine (600 [-LL,] 4.31 mmol) in [CH2C12] (6 [ML)] was added. This mixture was stirred overnight and then added to a separatory funnel with 100 mL of [CH2C12.] This solution was washed with 2 X 100 [ML] of 1 M aqueous HC1 and 100 [ML] of brine. The [CH2CK WAS] evaporated in the presence of silica gel, and the product was purified by chromatography using a Biotage Flash 40 M silica cartridge with a gradient from [CHUCK] to [1 % ETOAC] in [CH2C12 AS] eluent. Yield was 728 mg of white solid as the methyl ester. The methyl ester was hydrolyzed according to method D yielding 292 mg of white [SOLID. 1H] NMR (400 MHz, DMSO-d6) [8 12.] 57 (s, [1] H), 8. [80] (d, [J=] 8.7 Hz, [1 H),] 8.41-8. 44 (m, 2 H), 8.24 (d, [J=] 7.9 Hz, 1 H), 8.09- 8.14 (m, 2 H), 7.83 (t, J= 7.9 Hz, [1] H), 7.55 (d, J= 8.1 Hz, 1 [H),] 7.24 (t, J= 7.7 Hz, 1 H), 7.18 (d, [J=] 7.7 Hz, [1] H), 7.02 (t, [J=] 7.5 Hz, [1 H),] 3.73 (s, 2 H), 1. [08] (s, 6 H).
The synthetic route of 3,3-Dimethylindoline has been constantly updated, and we look forward to future research findings.
Reference:
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18414; (2004); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem