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Chemical Structure| 620592-45-2 Chemical Structure| 620592-45-2

Structure of 620592-45-2

Chemical Structure| 620592-45-2

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Product Details of [ 620592-45-2 ]

CAS No. :620592-45-2
Formula : C12H11NO3
M.W : 217.22
SMILES Code : O=C1CCC2=C1C([N+]([O-])=O)=C3CCCC3=C2
English Name :8-Nitro-3,5,6,7-tetrahydro-s-indacen-1(2H)-one
MDL No. :MFCD28975735
InChI Key :MKAURAAKBUQECD-UHFFFAOYSA-N
Pubchem ID :11769904

Safety of [ 620592-45-2 ]

Application In Synthesis of [ 620592-45-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 620592-45-2 ]

[ 620592-45-2 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 14927-64-1 ]
  • [ 620592-45-2 ]
  • [ 620592-44-1 ]
YieldReaction ConditionsOperation in experiment
1: 64% 2: 10% With sulfuric acid; nitric acid at 0℃; for 1h; 61.3; 62.3 Step 3: Synthesis of 8-nitro-2, 3 6, 7-tetrahydro-s-indacen-l (5H)-one & 4-nitro-2, 3 6, 7-tetrahydro-s- indacen- 1 (5H) -one To a solution of 3,5,6, 7-†etrahydro-2//-s-indacen-l-one (15.0 g, 87.09 mmol) in concentrated H28Q4 (75 mL) was added concentrated HNO3 (5 mL) slowly at 0°C. The resulting mixture was stirred at 0°C for 1 h. The reaction mixture was slowly added to ice water (100 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over anhydrous Na^SCfi, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (0-15 % EtOAc in petroleum ether) to give 8-nitro-3 ,5 ,6,7 ~tetrahydro-2if-s-indacen- 1 - one (12 g, 64% yield) and 4~nitro-3,5,6,7~ietrahydro-2//-s-indacen-l~one (1.8 g, 10% yield) both as white solid. H NMR (400 MHz, CDCI3) d = 7.46 (s, i l l). 3.15 - 3.11 (m, 2H), 3.05 (L ,/ 7.6 I lx. 2H), 3.00 (t,J = 7.6 Hz, 2H), 2.81 - 2.76 (m, 211). 2.25 - 2.15 (m, 2H). H NMR (400 MHz, CDC13) d = 7.83 (s, 1H), 3.57 - 3 46 (m, 3H), 3.42 (t, .7=7.6 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H), 2.82 - 2.76 (m, 2H), 2 26 - 2.20 (m, 2H).
1: 10% 2: 60% With sulfuric acid; nitric acid at 0℃; for 2h; 3; 1 Step 1: 4-nitro-2,3,6,7-tetrahydro-s-indacen-l(5H)-one Into a 1-L round-bottom flask was placed a solution of 1,2,3,5,6,7-hexahydro-s-indacen-l-one (40 g, 232 mmol) in H2SO4 (250 mL). Then HNO3 (29 g, 464 mmol) was added dropwise over 1 h at 0°C. The resulting solution was stirred for 1 hr at 0°C. The reaction mixture was slowly added to a mixture of water/ice (500 mL) and DCM (250 mL) with ice bath cooling. The organic layer was collected, dried over anhydrous Na2S04 and concentrated under vacuum. The crude product was purified by silica gel column with a gradient of ethyl acetate and petroleum ether (1 :50 to 1 : 1). This resulted in minor product 5 g (10%) of the title compound and major product 30 g (60%) of 8-nitro-2,3,6,7-tetrahydro-s-indacen-l(5H)-one both as a yellow solid.
With sulfuric acid; nitric acid at 0 - 5℃; for 2h;
With sulfuric acid; nitric acid at 0℃; for 2h; Overall yield = 90 percent; Overall yield = 90 g; A.3 Into a 1000-mL round-bottom flask was placed a solution of 1,2,3,5,6,7-hexahydro-s- indacen-l -one (80.0 g, 464.5 mmol ) in H2SO4 (500 mL). Then HNO3 (58.5 g, 929.0 mmol) was added dropwise over 1 h at 0°C. The resulting solution was stirred for 1 h at 0°C. The reaction mixture was slowly added to a mixture of v ater/ice (1000 mL) and DCM (500 mL) with ice bath cooling. The organic layer was collected, dried over Na?.S04 and concentrated under (2403) vacuum. This resulted in 90 0 g (90%) of the mixture of 4-nitro-l,2,3,5,6,7-hexahydro-s-indacen- 1-one and 8-nitro-2,3,6,7-tetrahydros-indacen-l(5H)-one as a yellow solid.
With sulfuric acid; nitric acid at 0 - 5℃; iii; iii Reaction Scheme 2 - Steps ii and iii (Method B) 3-Chloro-i-(2,3-dihydro-ifT-inden-5-yl)propan-i-one (12) (350 g) and cone sulfuric acid (5 vol, 3185 g) were charged into a round bottom flask at 25 ± 5 °C. The reaction mixture was heated to 70 ± 2°C and stirred for 8-10 hours. The absence of 3-chloro-i- (2,3-dihydro-ifT-inden-5-yl)propan-i-one (12) was confirmed by HPLC (Limit: < 2.0 %)· The reaction mixture was cooled to 0-5 °C. A nitration mixture was prepared from cone sulfuric acid (0.33 vol, 210.2 g) and cone. HN03 (0.5 vol, 248.5 g) at 10-15 °C. The nitration mixture was added to the above reaction mixture at 0-5 °C over a period of 45-60 minutes. The reaction mixture was maintained at 0-5 °C for 2 hours. The absence of 1,2,3,5,6,7-hexahydro-s-indacen-i-one (13) was confirmed by HPLC (Limit: < 2.0 %). After completion of the reaction, the reaction mixture was added into ice cold water (25 vol, 8.75 L) and maintained at 15 ± 10 °C for 1 hour. The product was extracted into ethyl acetate (1 x 10 vol: 3.5 L, 2 x 5 vol: 1.75 L). The combined organic layers were washed with 10% NaHC03 solution (10 vol, 3.5 L) at 25 ± 5 °C and dried over Na2S04 (175 g). The solvent was distilled off (up to 1 vol, 350 mL) under vacuum at below 45 °C and then co-distilled with n-heptane (2 vol, 700 mL) completely. n-Heptane (2 vol, 700 mL) was added and the reaction mixture was stirred for 1 hour at 25 ± 5 °C. The solid product was filtered, washed with n-heptane (0.5 vol, 175 mL) and dried under vacuum for 2 hours at 45-50 °C. The crude product was dissolved in methanol (2.0 vol, 700 mL) at 55-60 °C. Charcoal 5% was added and the reaction mixture was refluxed for 1 hour and then cooled to 45 °C. The reaction mixture was filtered through a hyflow bed and washed twice with methanol (2x (0.5 vol, 175 mL)). The filtrate was cooled to 0-5 °C and maintained for 2-3 hours at 0-5 °C. The solid product was filtered, washed with cold methanol (0.25 vol, 87.5 mL) and dried under vacuum for 3 hours at 45-50 °C. Final Product: 8-nitro-i,2,3,5,6,7-hexahydro-s-indacen-i-one (14) and 4- nitro-i,2,3,5,6,7-hexahydro-s-indacen-i-one (15) Brown solid Weight ratio of 14:15 was 7:1. Combined Output (14+15): 217 g Combined Yield (14+15): 60 % lH NMR (DMSO-d6; 400 MHz): 7.66 (s, lH), 3.08 (t, 2H), 2.98 (t, 2H) 2.88 (t, 2H), 2.72 (t, 2H) and 2.12 (m, 2H). Moisture content (by Karl Fischer titration): 0.72 HPLC purity: 96.44 %
With sulfuric acid; nitric acid In methanol at 0 - 5℃; Large scale; Overall yield = 62.24 percent; Overall yield = 38.87 kg; 2.iii Reaction scheme 2 - step (ii) and step (iii) The reaction mixture was maintained at o to 5 °C. Demineralised water (900.0 L) was charged at 25 to 30 °C into a 2.0 KL clean and dry glass-lined reactor. The water was cooled to o to 5 °C. The reaction mixture was added slowly added to the reactor at o to 5 °C. Toluene (480.0 L) was added and the temperature was raised to 30 to 35 °C. The reaction mixture was maintained at 30 to 35 °C for 30 minutes and allowed to settle at 30 to 35 °C for 30 minutes. The reaction mixture was filtered through a Celite bed (prepared with Celite (6.0 Kg) and toluene (30.0 L)). The Celite bed was washed with toluene (60.0 L). The solid was filtered and sucked dry for 30 min. The reaction mixture was charged to a 2.0 KL clean and dry glass-lined reactor. The reaction mixture was allowed to settle at 30 to 35 °C for 30 minutes. The layers were separated (aqueous layer (AL-1) and organic layer (OL-1)) and OL-1 was kept aside. Toluene (60.0 L) was charged to AL-1. The reaction mixture was stirred at 35 to 40 °C for 30 minutes and allowed to settle at 35 to 40 °C for 30 minutes. The layers were separated (aqueous layer (AL-2) and organic layer (OL-2)) and OL-2 was kept aside. OL-1 and OL-2 were combined to form OL-3. A 5 % saturated sodium bicarbonate solution (prepared from demineralised water (300.0 L) and sodium bicarbonate (15.0 Kg)) was slowly charged to OL-3 at 30 to 35 °C. The reaction mixture was stirred at 35 to 40 °C for 30 minutes and allowed to settle at 35 to 40 °C for 30 minutes. The reaction mixture was filtered through a Celite bed (prepared with Celite (6.0 Kg) and demineralised water (60.0 L)). The Celite bed was washed with toluene (60.0 L). The reaction mixture was charged to a 3.0 KL clean and dry glass-lined reactor. The reaction mixture was allowed to settle at 30 to 35 °C for 30 minutes. The layers were separated (aqueous layer (AL-3) and organic layer (OL-4)) and OL-4 was kept aside. Toluene (60.0 L) was charged to AL-3. The layers were separated (aqueous layer (AL-4) and organic layer (OL-5)) and OL-5 was kept aside. OL-4 and OL-5 were combined to form OL-6. Brine solution (prepared from demineralised water (300.0 L) and sodium chloride (12.0 Kg) at 25 to 30 °C. The reaction mixture was stirred at 30 to 35 °C for 30 minutes and allowed to settle at 30 to 35 °C for 30 minutes. The layers were separated (aqueous layer (AL-5) and organic layer (OL-7)) and OL-7 was kept aside. OL-7 was dried over anhydrous Na2SO4 (9.0 Kg) and the anhydrous Na2SO4 was washed with toluene (30.0 L) at 25 to 30 °C. The solvent was distilled under vacuum at below 40 to 45 °C until 5 % remained. Methanol (60.0 L) was charged to the reaction mixture at 40 to 45 °C and down to 60 L of reaction mass. Methanol (120.0 L) was charged to the reaction mixture at 40 to 45 °C and the reaction mixture was cooled to 5 to 10 °C and maintained at 5 to 10 °C for 30 minutes. The solid product was filtered, washed with cooled methanol (30.0 L), and dried in a hot air oven at 40 to 45 °C for 6 hours to afford the product. *1: To prepare the nitration mixture, sulfuric acid (27.0 L) was charged at 25 to 30 °C into a 160 L clean and dry glass-lined reactor. The reaction mixture was cooled to o to 5 °C. Nitric acid (27.0 L) at o to 5 °C was added slowly and the reaction mixture was maintained for 30 minutes at o to 5 °C to afford the nitration mixture. Final Product: 8-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one (11a) and 4- nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one (11b) Combined Output (11a+11b): 38.87 Kg Combined Yield (11a+11b): 62.24 % Weight ratio (11a:11b): 9:1 HPLC purity: 95.9% Moisture content: 0.19% 1H NMR: (500 MHz, CDCl3):h7.44(S, 1H), 2.2i(m, 2H), 2.78 (t, 2H), 3.02 (m, 4H), 3.13 (t, 2H)
With sulfuric acid; nitric acid at 0 - 5℃; Large scale; Overall yield = 62.24 percent; Overall yield = 38.87 kg; 2.c Reaction scheme 2 - step (b) and step (c) Then the reaction mixture was cooled to 0 to 5°C. A nitration mixture*1 was added slowly at 0 to 5°C and the reaction mixture was maintained at 0 to 5°C for 1 hour. The reaction mixture was maintained at 0 to 5°C. Demineralised water (900.0 L) was charged at 25 to 30°C into a 2.0 KL clean and dry glass-lined reactor. The water was cooled to 0 to 5°C. The reaction mixture was added slowly added to the reactor at 0 to 5°C. Toluene (480.0 L) was added and the temperature was raised to 30 to 35°C. The reaction mixture was maintained at 30 to 35°C for 30 minutes and allowed to settle at 30 to 35°C for 30 minutes. The reaction mixture was filtered through a Celite bed (prepared with Celite (6.0 Kg) and toluene (30.0 L)). The Celite bed was washed with toluene (60.0 L). The solid was filtered and sucked dry for 30 min. The reaction mixture was charged to a 2.0 KL clean and dry glass-lined reactor. The reaction mixture was allowed to settle at 30 to 35°C for 30 minutes. The layers were separated (aqueous layer (AL-1) and organic layer (OL-1)) and OL-1 was kept aside. Toluene (60.0 L) was charged to AL-1. The reaction mixture was stirred at 35 to 40°C for 30 minutes and allowed to settle at 35 to 40°C for 30 minutes. The layers were separated (aqueous layer (AL-2) and organic layer (OL-2)) and OL-2 was kept aside. OL-1 and OL-2 were combined to form OL-3. A 5 % saturated sodium bicarbonate solution (prepared from demineralised water (300.0 L) and sodium bicarbonate (15.0 Kg)) was slowly charged to OL-3 at 30 to 35°C. The reaction mixture was stirred at 35 to 40°C for 30 minutes and allowed to settle at 35 to 40°C for 30 minutes. The reaction mixture was filtered through a Celite bed (prepared with Celite (6.0 Kg) and demineralised water (60.0 L)). The Celite bed was washed with toluene (60.0 L). The reaction mixture was charged to a 3.0 KL clean and dry glass-lined reactor. The reaction mixture was allowed to settle at 30 to 35°C for 30 minutes. The layers were separated (aqueous layer (AL-3) and organic layer (OL-4)) and OL-4 was kept aside. Toluene (60.0 L) was charged to AL-3. The layers were separated (aqueous layer (AL-4) and organic layer (OL-5)) and OL-5 was kept aside. OL-4 and OL-5 were combined to form OL-6. Brine solution (prepared from demineralised water (300.0 L) and sodium chloride (12.0 Kg) at 25 to 30°C. The reaction mixture was stirred at 30 to 35°C for 30 minutes and allowed to settle at 30 to 35°C for 30 minutes. The layers were separated (aqueous layer (AL-5) and organic layer (OL-7)) and OL-7 was kept aside. OL-7 was dried over anhydrous Na2SO4 (9.0 Kg) and the anhydrous Na2SO4 was washed with toluene (30.0 L) at 25 to 30°C. The solvent was distilled under vacuum at below 40 to 45°C until 5 % remained. Methanol (60.0 L) was charged to the reaction mixture at 40 to 45°C and down to 60 L of reaction mass. Methanol (120.0 L) was charged to the reaction mixture at 40 to 45°C and the reaction mixture was cooled to 5 to 10°C and maintained at 5 to 10°C for 30 minutes. The solid product was filtered, washed with cooled methanol (30.0 L), and dried in a hot air oven at 40 to 45°C for 6 hours to afford the product. *1: To prepare the nitration mixture, sulfuric acid (27.0 L) was charged at 25 to 30°C into a 160 L clean and dry glass-lined reactor. The reaction mixture was cooled to 0 to 5°C. Nitric acid (27.0 L) at 0 to 5°C was added slowly and the reaction mixture was maintained for 30 minutes at 0 to 5°C to afford the nitration mixture. Final Product: 8-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one (11a) and 4-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one (11b) Combined Output (11a+11b): 38.87 Kg Combined Yield (11a+11b): 62.24 % Weight ratio (11a:11b): 9:1 HPLC purity: 95.9% Moisture content: 0.19% 1H NMR: (500 MHz, CDCl3):δ7.44(S, 1H), 2.21(m, 2H), 2.78 (t, 2H), 3.02 (m, 4H), 3.13 (t, 2H)
With sulfuric acid; nitric acid at 0 - 30℃; Sulfuric acid (300.0 L) was charged at 25 to 30 °C into a 2.0 KL clean and dry glass- lined reactor. 3-chloro-i-(2,3-dihydro-iH-inden-5-yl)propan-i-one (9) (60.0 Kg) was charged lot wise at 25 to 30 °C and the reaction mixture was maintained for 30 minutes at 25 to 30 °C. The reaction mixture was slowly heated to 65 to 70 °C and maintained at 65 to 70 °C for 24 hours. The absence of 3-chloro-i-(2,3-dihydro-iW-inden-5-yl)- propan-i-one (9) was confirmed by HPLC (Limit: Then the reaction mixture was cooled to o to 5 °C. A nitration mixture*1was added slowly at o to 5 °C and the reaction mixture was maintained at o to 5 °C for 1 hour. The absence of 1,2,3,5,6,7-hexahydro-s-indacen-i-one (10) was confirmed by HPLC (Limit: Demineralised water (900.0 L) was charged at 25 to 30 °C into a 2.0 KL clean and dry glass-lined reactor. The water was cooled to o to 5 °C. The reaction mixture was added slowly added to the reactor at o to 5 °C. Toluene (480.0 L) was added and the temperature was raised to 30 to 35 °C. The reaction mixture was maintained at 30 to 35 °C for 30 minutes and allowed to settle at 30 to 35 °C for 30 minutes. The reaction mixture was filtered through a Celite bed (prepared with Celite (6.0 Kg) and toluene (30.0 L)). The Celite bed was washed with toluene (60.0 L). The solid was filtered and sucked dry for 30 min. The reaction mixture was charged to a 2.0 KL clean and dry glass-lined reactor. The reaction mixture was allowed to settle at 30 to 35 °C for 30 minutes. The layers were separated (aqueous layer (AL-i) and organic layer (OL-i)) and OL-i was kept aside. Toluene (60.0 L) was charged to AL-i. The reaction mixture was stirred at 35 to 40 °C for 30 minutes and allowed to settle at 35 to 40 °C for 30 minutes. The layers were separated (aqueous layer (AL-2) and organic layer (OL-2)) and OL-2 was kept aside. OL-i and OL-2 were combined to form OL-3.A 5 % saturated sodium bicarbonate solution (prepared from demineralised water (300.0 L) and sodium bicarbonate (15.0 Kg)) was slowly charged to OL-3 at 30 to 35 °C. The reaction mixture was stirred at 35 to 40 °C for 30 minutes and allowed to settle at 35 to 40 °C for 30 minutes. The reaction mixture was filtered through a Celite bed (prepared with Celite (6.0 Kg) and demineralised water (60.0 L)). The Celite bed was washed with toluene (60.0 L). The reaction mixture was charged to a 3.0 KL clean and dry glass-lined reactor. The reaction mixture was allowed to settle at 30 to 35 °C for 30 minutes. The layers were separated (aqueous layer (AL-3) and organic layer (OL-4)) and OL-4 was kept aside.Toluene (60.0 L) was charged to AL-3. The layers were separated (aqueous layer (AL-4) and organic layer (OL-5)) and OL-5 was kept aside. OL-4 and OL-5 were combined to form OL-6. Brine solution (prepared from demineralised water (300.0 L) and sodium chloride (12.0 Kg) at 25 to 30 °C. The reaction mixture was stirred at 30 to 35 °C for 30 minutes and allowed to settle at 30 to 35 °C for 30 minutes. The layers were separated (aqueous layer (AL-5) and organic layer (OL-7)) and OL-7 was kept aside. OL-7 was dried over anhydrous Na2SO4(9.0 Kg) and the anhydrous Na2SO4was washed with toluene (30.0 L) at 25 to 30 °C. The solvent was distilled under vacuum at below 40 to 45 °C until 5 % remained. Methanol (60.0 L) was charged to the reaction mixture at 40 to 45 °C and down to 60 L of reaction mass. Methanol (120.0 L) was charged to the reaction mixture at 40 to 45 °C and the reaction mixture was cooled to 5 to 10 °C and maintained at 5 to 10 °C for 30 minutes. The solid product was filtered, washed with cooled methanol (30.0 L), and dried in a hot air oven at 40 to 45 °C for 6 hours to afford 38.87 Kg of a mixture of 8-nitro-i,2,3,5,6,7- hexahydro-s-indacen-i-one (11a) and 4-nitro-i,2,3,5,6,7-hexahydro-s-indacen-i-one (nb)Combined Yield (na+nb): 62.24 %Weight ratio (na:iib): 9:1HPLC purity: 95.9 %Moisture content: 0.19 % ‘H NMR: (500 MHz, CDC13): 8 7.44(8, 1H), 2.21(m, 2H), 2.78 (t, 2H), 3.02 (m, 4H), 3.13 Ct, 2H)*1: To prepare the nitration mixture, sulfuric acid (27.0 L) was charged at 25 to 30 °C into a 160 L clean and dry glass-lined reactor. The reaction mixture was cooled to o to 5 °C. Nitric acid (27.0 L) at o to 5 °C was added slowly and the reaction mixture was maintained for 30 minutes at o to 5 °C to afford the nitration mixture.
With sulfuric acid; nitric acid at 0 - 20℃; for 2h; Overall yield = 90 percent; Overall yield = 90 g; 3 Step 3: Mixture of 4-nitro-2,3,6,7-tetrahydros-indacen-1(5H)-one and 8-nitro-2,3,6,7- tetrahydros-indacen-1(5H)-one To a stirred solution of 1,2,3,5,6,7-hexahydro-s-indacen-1-one (80 g, 464.5 mmol) in H2SO4 (500 mL) was added HNO3(58.5 g, 929 mmol) dropwise over 1 h at 0 °C. The resulting solution was stirred for 1 h at RT. The reaction mixture was slowly added to a mixture of water/ice (1000 mL) and DCM (500 mL) with ice bath cooling. The organic layer was collected, dried over Na2SO4 and concentrated under vacuum. This resulted in 90 g (90%) of the mixture of 4-nitro-1,2,3,5,6,7- hexahydro-s-indacen-1-one and 8-nitro-2,3,6,7-tetrahydro-s-indacen-1(5H)-one as a yellow solid. MS-ESI: 218 (M+1).

  • 2
  • [ 496-11-7 ]
  • [ 620592-45-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 78 percent / AlCl3 / CH2Cl2 / -10 - 20 °C 2: H2SO4 / 48 h / 55 - 60 °C 3: HNO3; H2SO4 / 2 h / 0 - 5 °C
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / dichloromethane / 2 h / 20 °C 2.1: sulfuric acid / 48 h / 55 - 60 °C 2.2: 1 h / 0 - 5 °C
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 16.5 h / -10 - 20 °C 2: sulfuric acid / 16 h / 55 °C 3: sulfuric acid; nitric acid / 2 h / 0 °C
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 2 h / -10 - 27 °C / Inert atmosphere 2: sulfuric acid / water / 12 h / 70 °C 3: sulfuric acid; nitric acid / 1 h / 0 - 10 °C
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / dichloromethane / 8 h / 0 - 10 °C / Large scale 2.1: sulfuric acid / 48 h / 55 °C 2.2: 2 h / 0 - 10 °C
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 8 h / 0 - 10 °C / Large scale 2: sulfuric acid / 40 h / 55 °C 3: sulfuric acid; nitric acid / 1 h / 0 °C
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 2 h / 0 - 20 °C 2: sulfuric acid / dichloromethane / Reflux 3: sulfuric acid; nitric acid / dichloromethane / 3 h / 0 °C

  • 3
  • [ 39105-39-0 ]
  • [ 620592-45-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: H2SO4 / 48 h / 55 - 60 °C 2: HNO3; H2SO4 / 2 h / 0 - 5 °C
Multi-step reaction with 2 steps 1: sulfuric acid / 16 h / 55 °C 2: sulfuric acid; nitric acid / 2 h / 0 °C
Multi-step reaction with 2 steps 1: sulfuric acid / water / 12 h / 70 °C 2: sulfuric acid; nitric acid / 1 h / 0 - 10 °C
Multi-step reaction with 2 steps 1: sulfuric acid / 40 h / 55 °C 2: sulfuric acid; nitric acid / 1 h / 0 °C
Multi-step reaction with 2 steps 1: sulfuric acid / dichloromethane / Reflux 2: sulfuric acid; nitric acid / dichloromethane / 3 h / 0 °C

  • 4
  • [ 620592-45-2 ]
  • [ 1995073-34-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 10% Pd/C; hydrogen / methanol / 2 h / 20 °C 2.1: dmap / acetonitrile / 0.08 h / 20 °C 2.2: 0.5 h / 20 °C 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 3.2: 16 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 3 steps 1.1: 10% Pd/C; hydrogen / methanol / 2 h / 20 °C / 760.05 Torr / Inert atmosphere 2.1: dmap / acetonitrile / 0.08 h / 20 °C 2.2: 0.5 h / 20 °C 3.1: sodium hydride / acetonitrile; tetrahydrofuran / 0.5 h / 0 - 20 °C / Inert atmosphere 3.2: 16 h / 0 - 20 °C / Inert atmosphere
  • 5
  • [ 620592-45-2 ]
  • [ 1995073-30-7 ]
YieldReaction ConditionsOperation in experiment
93% With 10% Pd/C; hydrogen In methanol at 20℃; for 2h; A solution of 8-nitro-3,5,6,7-tetrahydro-s-indacen-1 (2H)-one (200 mg, 0.92 mmol) in MeOH (5 mL) was degassed with nitrogen for 5 minutes, 10% Pd/C (20 mg, 10% wt/wt) was added and the mixture stirred under hydrogen atmosphere at room temperature for 2 h. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo to give 8-amino- 3,5,6,7-tetrahydro-s-indacen-1 (2H)-one as off an white solid (160 mg, 93%).1H NMR (600 MHz, DMSO-afe) δ 6.49 (s, 1 H), 6.34 (s, 2H), 2.90-2.84 (m, 2H), 2.80 (t, J = 7.5 Hz, 2H), 2.62 (t, J = 7.4 Hz, 2H), 2.56-2.51 (m, 2H), 2.04-1 .99 (m, 2H).13C NMR (150 MHz, DMSO-afe): 206.6, 155.4, 153.7, 144.1 , 125.3, 1 18.6, 109.4, 36.8, 33.7, 28.6, 25.0, 24.9. LCMS (m/z): 188 [M+H]+. HRMS calculated for C2H14N10i[M+H]+188.1070, found 188.1077.
93% With 10% Pd/C; hydrogen In methanol at 20℃; for 2h; Inert atmosphere;
91.2% With 10 wt.% Pd/C; hydrogen at 20℃; for 2h; 1 Step 1: 8-Amino-3,5,6,7-tetrahydro-s-indacen-l(2H)-one Into a 250-mL round-bottom flask purged and maintained with an inert atmosphere of hydrogen, was placed a solution of 8-nitro-l,2,3,5,6,7-hexahydro-s-indacen-l-one (700 mg, 3.22 mmol) in MeOH (10 mL), and Pd/C (10% wt, 100 mg). The flask was evacuated and flushed three times with hydrogen. The resulting solution was stirred for 2 h at RT under an atmosphere of hydrogen. The Pd/C catalysts were filtered out, and the filtrate was concentrated under vacuum. This resulted in 550 mg (91.2%) of the title compound as a yellow oil. MS-ESI: 188 (M+l).
  • 6
  • [ 620592-45-2 ]
  • [ 1995073-32-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: 10% Pd/C; hydrogen / methanol / 2 h / 20 °C 2.1: dmap / acetonitrile / 0.08 h / 20 °C 2.2: 0.5 h / 20 °C
Multi-step reaction with 2 steps 1.1: 10% Pd/C; hydrogen / methanol / 2 h / 20 °C / 760.05 Torr / Inert atmosphere 2.1: dmap / acetonitrile / 0.08 h / 20 °C 2.2: 0.5 h / 20 °C
  • 7
  • [ 620592-45-2 ]
  • [ 1995069-04-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: 10% Pd/C; hydrogen / methanol / 2 h / 20 °C 2.1: dmap / acetonitrile / 0.08 h / 20 °C 2.2: 0.5 h / 20 °C 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 3.2: 16 h / 0 - 20 °C / Inert atmosphere 4.1: methanol; sodium tetrahydroborate / 3 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: 10% Pd/C; hydrogen / methanol / 2 h / 20 °C / 760.05 Torr / Inert atmosphere 2.1: dmap / acetonitrile / 0.08 h / 20 °C 2.2: 0.5 h / 20 °C 3.1: sodium hydride / acetonitrile; tetrahydrofuran / 0.5 h / 0 - 20 °C / Inert atmosphere 3.2: 16 h / 0 - 20 °C / Inert atmosphere 4.1: sodium tetrahydroborate / methanol / 3 h / 0 - 20 °C / Inert atmosphere
  • 8
  • [ 39105-39-0 ]
  • [ 2014359-78-3 ]
  • [ 620592-45-2 ]
  • [ 620592-44-1 ]
YieldReaction ConditionsOperation in experiment
1: 42% 2: 11% 3: 5% Stage #1: 3-chloro-1-(2,3-dihydro-1H-inden-5-yl)propan-1-one With sulfuric acid at 55 - 60℃; for 48h; Stage #2: With sulfuric acid; nitric acid at 0 - 5℃; for 1h;
1: 36% 2: 5% 3: 3.5% Stage #1: 3-chloro-1-(2,3-dihydro-1H-inden-5-yl)propan-1-one With sulfuric acid at 60℃; for 48h; Stage #2: With sulfuric acid; nitric acid at 0 - 5℃; 2 Step 2. Mixture of 8-nitro- 1,2,3, 5,6, 7-hexahydro-s-indacen-l -one (Intermediate lb), 4-nitro- 1.2.3.5.6.7- hexahydro-s-indacen-1-one (Intermediate 1c) and 5-nitro-l,2,3,6,7,8- hexahydroas-indacen-3-one (Intermediate 1d) 3-chloro-1-(2,3-dihydro-lH-inden-5-yl)propan-1-one (Intermediate la) (82 g, 0.39 mol) was added portion wise as a solid to a concentrated sulfuric acid (71 ml, 1.34 mol). The resulting mixture was heated to 60 °C for two days. Then RM was cooled to 0 °C and a mixture of nitric acid (26 ml, 0.59 mol) and sulfuric acid (26 ml, 0.49 mol) was added dropwise. RM was stirred for one hour, temperature was kept between 0 °C and 5 °C. The RM was slowly added to a mixture of water and DCM with ice bath cooling. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layers were washed with brine and saturated sodium bicarbonate. The organic layers were dried over Na2S04 and filtered. The crude mixture was purified by FCC (hexane/ethyl acetate). Obtained fractions was crystallized from MeOH. Obtained: 8-nitro- 1,2,3, 5, 6, 7-hexahydro-s-indacen-l -one (Intermediate lb), (30.77g; 0.14 mol; 36 %) UPLC-MS: purity 98 %, 218 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.67 (s, 1H), 3.15 - 3.08 (m, 2H), 3.04 (t, J = 7.5 Hz, 2H), 2.90 (t, J = 7.5 Hz, 2H), 2.77 - 2.71 (m, 2H), 2.13 (p, J = 7.5 Hz, 2H); 4-nitro-l,2,3,5,6,7-hexahydro-s- indacen-1-one (Intermediate lc), (5.19 g; 0.02 mol; 5 %) UPLC-MS: purity 100 %, 218 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.82 (s, 1H), 3.41 - 3.36 (m, 2H), 3.34 - 3.29 (m, 3H), 3.02 (t, J = 7.5 Hz, 2H), 2.77 - 2.69 (m, 2H), 2.13 (p, J = 7.6 Hz, 2H); 5-nitro- 1.2.3.6.7.8- hexahydroas-indacen-3-one (Intermediate Id), (3.00 g; 0.01 mol; 3.5 %) UPLC-MS: purity 100 %, 218 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 1H), 3.39 (t, J = 7.6 Hz, 2H), 3.14 - 3.09 (m, 2H), 3.01 (t, J = 7.7 Hz, 2H), 2.81 - 2.73 (m, 2H), 2.19 (p, J = 7.7 Hz, 2H).
1: 36% 2: 5% 3: 4% Stage #1: 3-chloro-1-(2,3-dihydro-1H-inden-5-yl)propan-1-one With sulfuric acid at 60℃; for 48h; Stage #2: With nitric acid at 0 - 5℃; for 1h; 2 Mixture of 8-nitro-l,2,3,5,6,7-hexahydro-s-indacen-l-one, 4-nitro-l,2,3,5,6,7-hexahydro-s- indacen-l-one and 5-nitro-l,2,3,6,7,8-hexahydroas-indacen-3-one 3-chloro-l-(2,3-dihydro-lH-inden-5-yl)propan-l-one (82 g, 0.39 mol) was added portion wise to concentrated sulfuric acid (71 ml, 1.34 mol). The resulting mixture was heated to 60°C for 2 days. The RM was cooled to 0°C and a mixture of nitric acid (26 ml, 0.59 mol) and sulfuric acid (26 ml, 0.49 mol) was added dropwise. The RM was stirred at a temperature between 0°C and 5°C for 1 h. The RM was slowly added to a mixture of water and DCM with ice bath cooling. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layers were washed sequentially with brine and saturated sodium bicarbonate. The organic layers were dried over Na2SO4and filtered. The crude mixture was purified by FCC (hexane/ethyl acetate). The products were further purified by crystallisation from MeOH to give the desired products.8-nitro-l,2,3,5,6,7-hexahydro-s-indacen-l-one:Y= 36 %MS ES+: 2181H NMR (400 MHz, DMSO-d6) δ 7.67 (s, 1H), 3.15 - 3.08 (m, 2H), 3.04 (t, J = 8 Hz, 2H), 2.90 (t, J = 8 Hz, 2H), 2.77 - 2.71 (m, 2H), 2.17 - 2.10 (m, 2H).4-nitro-l,2,3,5,6,7-hexahydro-s-indacen-l-one:Y= 5 %MS ES+: 2181H NMR (400 MHz, DMS0-d6) δ 7.82 (s, 1H), 3.41 - 3.36 (m, 2H), 3.34 - 3.29 (m, 3H), 3.02 (t, J = 8 Hz, 2H), 2.77 - 2.69 (m, 2H), 2.17 - 2.10 (m, 2H). 5-nitro-l,2,3,6,7,8-hexahydroas-indacen-3-one:Y = 4 %MS ES+: 2181H NMR (400 MHz, DMS0-d6) δ 8.09 (s, 1H), 3.39 (t, J = 8 Hz, 2H), 3.14 - 3.09 (m, 2H), 3.01 (t, J = 8 Hz, 2H), 2.81 - 2.73 (m, 2H), 2.23 - 2.15 (m, 2H).
  • 9
  • [ 620592-45-2 ]
  • [ 2014359-79-4 ]
YieldReaction ConditionsOperation in experiment
97% With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h; Inert atmosphere;
94% With methanol; sodium tetrahydroborate at 0 - 20℃; for 1h; Inert atmosphere; 153.1; 154.1; 155.1; 156.1 Step 1 - Synthesis of 8-nitro- l ,2,3,5,6,7-hexahydro-s-indacen-l -ol : To a solution of 8-nitro-3,5,6,7-tetrahydro-2iT-5-indacen-l-one (7.9 g, 36.37 mmol) in MeOH (100 mL) was added NaBH4 (6.9 g, 181.84 mmol) at 0°C under a nitrogen atmosphere. After addition, the reaction was warmed to room temperature. After 1 hour, the solvent was removed in vacuo and H20 (10 mL) was added to the crude residue. The aqueous layer was extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over Na2S04, filtered and concentrated. The crude residue was purified by silica gel column chromatography (15% EtOAc in petroleum ether) to give 8-nitro-l,2,3,5,6,7-hexahydro- s-indacen-l-ol (7.5 g, yield: 94%) as a light yellow oil.
  • 10
  • [ 620592-45-2 ]
  • [ 2014359-80-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / Molecular sieve; Reflux; Dean-Stark
Multi-step reaction with 2 steps 1: methanol; sodium tetrahydroborate / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / 110 °C / Dean-Stark
  • 11
  • [ 620592-45-2 ]
  • [ 2014359-81-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / Molecular sieve; Reflux; Dean-Stark 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: methanol; sodium tetrahydroborate / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / 110 °C / Dean-Stark 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere
  • 12
  • [ 620592-45-2 ]
  • [ 2014359-82-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / Molecular sieve; Reflux; Dean-Stark 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 4: zinc(II) iodide; sodium cyanoborohydride / 1,2-dichloro-ethane / 4 h / Reflux
Multi-step reaction with 4 steps 1: methanol; sodium tetrahydroborate / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / 110 °C / Dean-Stark 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere 4: zinc(II) iodide; sodium cyanoborohydride / 1,2-dichloro-ethane / 4 h / 80 °C
  • 13
  • [ 620592-45-2 ]
  • [ 2014359-83-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / toluene / 2 h / Molecular sieve; Reflux; Dean-Stark 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 4: zinc(II) iodide; sodium cyanoborohydride / 1,2-dichloro-ethane / 4 h / Reflux 5: 10% Pd/C; hydrogen / methanol / 16 h / 20 °C / 760.05 Torr / Inert atmosphere
  • 14
  • [ 620592-45-2 ]
  • [ 2915317-30-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C / Inert atmosphere 2.1: toluene-4-sulfonic acid / toluene / 2 h / Molecular sieve; Reflux; Dean-Stark 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 4.1: zinc(II) iodide; sodium cyanoborohydride / 1,2-dichloro-ethane / 4 h / Reflux 5.1: 10% Pd/C; hydrogen / methanol / 16 h / 20 °C / 760.05 Torr / Inert atmosphere 6.1: dmap / acetonitrile / 0.08 h / 20 °C 6.2: 0.5 h / 20 °C
 

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