2,3,3a,4,5,6,7,7a-octahydro-1H-isoindole

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hexahydro-1H-isoindole-1,3(2H)-dione (1.0 g, 6.5 mmol) in dry THF (14 mL) was added dropwise to a stirred slurry of LiAlH4 in dry THF (6 mL) at such a rate that the solvent gentle refluxed. The resulting reaction mixture was heated to reflux for 20 h and then allowed to cool to RT. The reaction mixture was cooled with an ice-bath, and H2O (1 mL), a 20% aqueous solution of NaOH (2.5 mL) and H2O (2 mL) were sequentially added. The mixture was filtered and THF removed under reduced pressure. The aqueous phase was extracted with Et2O, and the separated organics were dried over Na2SO4, filtered and concentrated to dryness, affording the title compound (690 mg, 5.52 mmol) as a white powder that was used in the next step without any further purification. The resulting reaction mixture was heated to reflux for 20 h The reaction mixture was cooled with an ice-bath The mixture was filtered THF removed under reduced pressure The aqueous phase was extracted with Et2O the separated organics were dried over Na2SO4 filtered concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hexahydro-1H-isoindole-1,3(2H)-dione (1.0 g, 6.5 mmol) in dry THF (14 mL) was added dropwise to a stirred slurry of LiAlH4 in dry THF (6 mL) at such a rate that the solvent gentle refluxed. The resulting reaction mixture was heated to reflux for 20 h and then allowed to cool to RT. The reaction mixture was cooled with an ice-bath, and H2O (1 mL), a 20% aqueous solution of NaOH (2.5 mL) and H2O (2 mL) were sequentially added. The mixture was filtered and THF removed under reduced pressure. The aqueous phase was extracted with Et2O, and the separated organics were dried over Na2SO4, filtered and concentrated to dryness, affording the title compound (690 mg, 5.52 mmol) as a white powder that was used in the next step without any further purification. The resulting reaction mixture was heated to reflux for 20 h The reaction mixture was cooled with an ice-bath The mixture was filtered THF removed under reduced pressure The aqueous phase was extracted with Et2O the separated organics were dried over Na2SO4 filtered concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-phenylbutanoic acid (4.86 g, 0.02 mol) and thionyl chloride (2.2 mL, 0.03 mol) were refluxed in dichloromethane (100 mL) under nitrogen for 3 hours. The solution was evaporated and flushed with benzene three times. The residue was dissolved in diethyl ether (50 mL) and cooled in an ice bath. Octahydroisoindole (2.5 g, 0.02 mol) and diisopropylethylamine (3.5 mL, 0.02 mol) dissolved in diethyl ether (50 mL) were added and the reaction was stirred for 60 hours at room temperature. TLC (Uniplate/EtOAc) showed essentially complete reaction. The solution was washed with water, sat. NaHCO3, and dried (Na2SO4). Evaporation of solvent left crude product. The solution was evaporated flushed with benzene three times The residue was dissolved in diethyl ether (50 mL) cooled in an ice bath were added reaction The solution was washed with water, sat. NaHCO3 dried (Na2SO4) Evaporation of solvent left crude product

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-phenylbutanoic acid (4.86 g, 0.02 mol) and thionyl chloride (2.2 mL, 0.03 mol) were refluxed in dichloromethane (100 mL) under nitrogen for 3 hours. The solution was evaporated and flushed with benzene three times. The residue was dissolved in diethyl ether (50 mL) and cooled in an ice bath. Octahydroisoindole (2.5 g, 0.02 mol) and diisopropylethylamine (3.5 mL, 0.02 mol) dissolved in diethyl ether (50 mL) were added and the reaction was stirred for 60 hours at room temperature. TLC (Uniplate/EtOAc) showed essentially complete reaction. The solution was washed with water, sat. NaHCO3, and dried (Na2SO4). Evaporation of solvent left crude product. The solution was evaporated flushed with benzene three times The residue was dissolved in diethyl ether (50 mL) cooled in an ice bath were added reaction The solution was washed with water, sat. NaHCO3 dried (Na2SO4) Evaporation of solvent left crude product

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]nonane (F); spiro[bicyclo[2.2.1]heptane-2,3'-pyrrolidine] (G); spiro[bicyclo[2.2.2]octane-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]-pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6a-hexahydrocyclopenta[b]pyrrole (O); all of which can optionally be substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hexahydro-1H-isoindole-1,3(2H)-dione (1.0 g, 6.5 mmol) in dry THF (14 mL) was added dropwise to a stirred slurry of LiAlH4 in dry THF (6 mL) at such a rate that the solvent gentle refluxed. The resulting reaction mixture was heated to reflux for 20 h and then allowed to cool to RT. The reaction mixture was cooled with an ice-bath, and H2O (1 mL), a 20% aqueous solution of NaOH (2.5 mL) and H2O (2 mL) were sequentially added. The mixture was filtered and THF removed under reduced pressure. The aqueous phase was extracted with Et2O, and the separated organics were dried over Na2SO4, filtered and concentrated to dryness, affording the title compound (690 mg, 5.52 mmol) as a white powder that was used in the next step without any further purification. The resulting reaction mixture was heated to reflux for 20 h The reaction mixture was cooled with an ice-bath The mixture was filtered THF removed under reduced pressure The aqueous phase was extracted with Et2O the separated organics were dried over Na2SO4 filtered concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-phenylbutanoic acid (4.86 g, 0.02 mol) and thionyl chloride (2.2 mL, 0.03 mol) were refluxed in dichloromethane (100 mL) under nitrogen for 3 hours. The solution was evaporated and flushed with benzene three times. The residue was dissolved in diethyl ether (50 mL) and cooled in an ice bath. Octahydroisoindole (2.5 g, 0.02 mol) and diisopropylethylamine (3.5 mL, 0.02 mol) dissolved in diethyl ether (50 mL) were added and the reaction was stirred for 60 hours at room temperature. TLC (Uniplate/EtOAc) showed essentially complete reaction. The solution was washed with water, sat. NaHCO3, and dried (Na2SO4). Evaporation of solvent left crude product. The solution was evaporated flushed with benzene three times The residue was dissolved in diethyl ether (50 mL) cooled in an ice bath were added reaction The solution was washed with water, sat. NaHCO3 dried (Na2SO4) Evaporation of solvent left crude product