2-amino-6,7,8,9-tetrahydrobenzo[7]annulen-5-one

To mechanically-stirred polyphosphoric acid (2000 g) at 100° C. was added in portions over several min E28B (93.2 g, 396 mmol). The mixture then was stirred at 100° C. for 3 h. At this point external heating was discontinued. While the reaction mixture was still hot water-ice was added in small portions such that the temperature remained at 80-100° C. [Note: this addition is initially very exothermic. External cooling was employed as needed to help keep the temperature in the desired range.]The addition of water-ice was continued until the total reaction volume was 4500 mL. By this time the mixture had cooled to 0-10° C. With external cooling, 50percent aqueous sodium hydroxide solution was added at a rate such that the reaction temperature remained at <35° C. This addition was continued until the aqueous mixture reached pH 3-4. The mixture then was extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Column chromatography of the residue on silica gel (elution: 0-5percent diethyl ether/methylene chloride), followed by crystallization of the material from methylene chloride/hexane, provided 58.5 g (84percent) of E28C: NMR (300 MHz, CDClTo mechanically-stirred polyphosphoric acid (2000 g) at 100° C. was added in portions over several min E28B (93.2 g, 396 mmol). The mixture then was stirred at 100° C. for 3 h. At this point external heating was discontinued. While the reaction mixture was still hot water-ice was added in small portions such that the temperature remained at 80-100° C. [Note: this addition is initially very exothermic. External cooling was employed as needed to help keep the temperature in the desired range.]The addition of water-ice was continued until the total reaction volume was 4500 mL. By this time the mixture had cooled to 0-10° C. With external cooling, 50percent aqueous sodium hydroxide solution was added at a rate such that the reaction temperature remained at <35° C. This addition was continued until the aqueous mixture reached pH 3-4. The mixture then was extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Column chromatography of the residue on silica gel (elution: 0-5percent diethyl ether/methylene chloride), followed by crystallization of the material from methylene chloride/hexane, provided 58.5 g (84percent) of E28C: NMR (300 MHz, CDClA mixture of 2-chloro-6, 7, 8, 9-tetrahydro-5H-benzo[7]annulen-5-one (11.3 g, 58 mmol), tert- butyl carbamate (8.83 g, 75.4 mmol), CS2CO3 (37.8 g, 116 mmol), tris(dibenzylideneacetone) dipalladium(O) (800 mg, 0.87 mmol) and tri-ieri-butylphosphonium tetrafluoroborate (1.0 g, 3.5 mmol) in 1, 4-dioxane (200 mL) was stirred under N2 at 90 C for 18 h. The mixture was partitioned between EtOAc (800 mL) and H20 (800 mL). The organic layer was washed with brine, dried over Na2S04, filtered and concentrated. The residue was chromatographed on silica gel, eluting with 0-25% EtOAc in hexanes to afford 13.5 g of oil that was dissolved in trifluoroacetic acid (20 mL). The solution was stirred at room temperature for 20 min before removing all volatiles with a stream of nitrogen. The residue was partitioned in CH2C12 (500 mL) and aqueous saturated NaHC03 (500 mL). The organic layer was dried over Na2S04, filtered and concentrated to afford 8.0 g (79%) of product. LC-MS: 176.1 [M+H]+, RT 0.95 min.

Molecular Weight:175.23
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:175.099714038
Monoisotopic Mass:175.099714038
Topological Polar Surface Area:43.1
Heavy Atom Count:13
Complexity:202
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes