4-bromo-2,3-dihydro-1H-inden-1-ol

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

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

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

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

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

Procedure: To a solution of the crude 4-bromo-1-indanol (1.02 g) in dimethylformamide (10 ml) were added at an ice temperature imidazole (0.645 g) and tert-butyldimethylsilyl chloride (0.857 g). The reaction mixture was stirred at the same temperature overnight, poured into a saturated aqueous saline solution and extracted with ether. The organic layer was washed with a saturated aqueous saline, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residual concentrate (1.6 g) was purified by chromatography on a silica gel column to give the title compound (1.51 g). poured into a saturated aqueous saline solution extracted with ether The organic layer was washed with a saturated aqueous saline dried over sodium sulfate the solvent was removed by distillation under reduced pressure The residual concentrate (1.6 g) was purified by chromatography on a silica gel column

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

Procedure: To a solution of 4-bromo-1-indanone (1.0 g) in a mixture of ethanol (6 ml) and tetrahydrofuran (3 ml) was added sodium borohydride (0.09 g) at an ice temperature. The reaction mixture was stirred at the same temperature overnight and poured into dilute hydrochloric acid, and the aqueous layer was saturated with saline and extracted with ether. The organic layer was washed with a saturated aqueous saline, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residual concentrate (1.02 g) thus obtained was used for the next reaction without further purification. extracted with ether The organic layer was washed with a saturated aqueous saline dried over sodium sulfate the solvent was removed by distillation under reduced pressure The residual concentrate (1.02 g) thus obtained was used for the next reaction without further purification

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

Procedure: To a solution of 4-bromo-2,3-dihydro-1H-inden-1-ol INT-28 (2.56 g, 12.0 mm) in DMF (5 mL) were added TBDMSCl (2.17 g, 14.4 mmol) and imidazole (2 g, 30.0 mmol) and the reaction mixture stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with EA. The organic layers were washed with water and brine, and dried over MgSO4. The crude product was purified by chromatography (EA/hexane) to afford (4-bromo-2,3-dihydro-1H-inden-1-yloxy)(tert-butyl)dimethylsilane INT-29 (3.3 g, 84%) as a clear oil. LCMS-ESI (m/z) calculated for C15H23BrOSi: 327.3; found 195.0 [M−OTBS]+, tR=3.07 min. 1H NMR (400 MHz, CDCl3) δ 7.20 (d, J=7.8 Hz, 1H), 7.06 (d, J=7.4 Hz, 1H), 6.92 (t, J=7.7 Hz, 1H), 5.13 (t, J=7.0 Hz, 1H), 2.85 (ddd, J=16.4, 9.1, 2.9 Hz, 1H), 2.57 (dt, J=16.5, 8.3 Hz, 1H), 2.36-2.17 (m, 1H), 1.76 (dtd, J=12.8, 8.8, 7.1 Hz, 1H), 0.83-0.72 (m, 9H), 0.05-−0.06 (m, 6H). extracted with EA The organic layers were washed with water and brine dried over MgSO4 The crude product was purified by chromatography (EA/hexane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of 4-bromoindanone (3 g, 14.2 mmol) in anhydrous EtOH (30 mL) were added sodium borohydride (0.36 g, 9.5 mmol) and silica gel (2 g) at 0° C. The reaction was stirred at 0° C. for 20 min and was allowed to stir at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 and concentrated to remove EtOH. The aqueous layer was extracted with EA and the organic phase was dried over MgSO4. After concentration, the crude product was purified by chromatography (EA/hexane) to yield 4-bromo-2,3-dihydro-1H-inden-1-ol INT-28 (2.56 g, 85%) as white solid. LCMS-ESI (m/z) calculated for C9H9BrO: 213.1; found 195.0 [M−H2O]+, tR=3.07 min. 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J=7.9, 1H), 7.27 (d, J=7.4, 1H), 7.05 (t, J=7.7, 1H), 5.23 (t, J=6.2, 1H), 3.00 (ddd, J=16.6, 8.8, 4.6, 1H), 2.84-2.66 (m, 1H), 2.45 (dddd, J=13.2, 8.4, 7.0, 4.6, 1H), 1.96-1.70 (m, 2H). to stir at room temperature for 2 h The reaction mixture was quenched with saturated NaHCO3 concentrated to remove EtOH The aqueous layer was extracted with EA the organic phase was dried over MgSO4 After concentration the crude product was purified by chromatography (EA/hexane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of 4-bromoindanone (3 g, 14.2 mmol) in anhydrous EtOH (30 mL) were added sodium borohydride (0.36 g, 9.5 mmol) and silica gel (2 g) at 0° C. The reaction was stirred at 0° C. for 20 min and was allowed to stir at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 and concentrated to remove EtOH. The aqueous layer was extracted with EA and the organic phase was dried over MgSO4. After concentration, the crude product was purified by chromatography (EA/hexane) to yield 4-bromo-2,3-dihydro-1H-inden-1-ol INT-28 (2.56 g, 85%) as white solid. LCMS-ESI (m/z) calculated for C9H9BrO: 213.1; found 195.0 [M−H2O]+, tR=3.07 min. 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J=7.9, 1H), 7.27 (d, J=7.4, 1H), 7.05 (t, J=7.7, 1H), 5.23 (t, J=6.2, 1H), 3.00 (ddd, J=16.6, 8.8, 4.6, 1H), 2.84-2.66 (m, 1H), 2.45 (dddd, J=13.2, 8.4, 7.0, 4.6, 1H), 1.96-1.70 (m, 2H). to stir at room temperature for 2 h The reaction mixture was quenched with saturated NaHCO3 concentrated to remove EtOH The aqueous layer was extracted with EA the organic phase was dried over MgSO4 After concentration the crude product was purified by chromatography (EA/hexane)

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

Procedure: Compound 3 (150 g, 704 mmol, 1 equiv) was suspended in a mixture of concentrated sulfuric acid (250 mL) and water (1.25 L). The mixture was refluxed overnight. The reaction was cooled and extracted with 1.5 L of dichloromethane. The organic layer was washed with saturated sodium bicarbonate (1.5 L), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified over silica gel (800 g), eluting with heptanes to give compound 4 (95 g, 69% yield) as a light yellow oil. The mixture was refluxed overnight The reaction was cooled extracted with 1.5 L of dichloromethane The organic layer was washed with saturated sodium bicarbonate (1.5 L) dried over sodium sulfate concentrated under reduced pressure The residue was purified over silica gel (800 g) eluting with heptanes

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

Procedure: Compound 3 (150 g, 704 mmol, 1 equiv) was suspended in a mixture of concentrated sulfuric acid (250 mL) and water (1.25 L). The mixture was refluxed overnight. The reaction was cooled and extracted with 1.5 L of dichloromethane. The organic layer was washed with saturated sodium bicarbonate (1.5 L), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified over silica gel (800 g), eluting with heptanes to give compound 4 (95 g, 69% yield) as a light yellow oil. The mixture was refluxed overnight The reaction was cooled extracted with 1.5 L of dichloromethane The organic layer was washed with saturated sodium bicarbonate (1.5 L) dried over sodium sulfate concentrated under reduced pressure The residue was purified over silica gel (800 g) eluting with heptanes

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

Procedure: A solution of compound 2 (435 g, 2.06 mol, 1 equiv) in ethanol (5 L) was treated with sodium borohydride (101.6 g, 2.68 mol, 1.3 equiv) and stirred overnight at room temperature. The reaction was concentrated under reduced pressure and the residue partitioned between 4 L of dichloromethane and 4 L of 10% aqueous hydrochloric acid. The layers were separated and the aqueous layer was extracted with dichloromethane (3×1 L). The combined organic layers were washed with saturated brine (2 L), dried over sodium sulfate and concentrated under reduced pressure. The resulting solid was dried overnight in a vacuum oven at 30° C. to give compound 3 (422 g, 96% yield) as an off-white solid. The reaction was concentrated under reduced pressure the residue partitioned between 4 L of dichloromethane and 4 L of 10% aqueous hydrochloric acid The layers were separated the aqueous layer was extracted with dichloromethane (3×1 L) The combined organic layers were washed with saturated brine (2 L) dried over sodium sulfate concentrated under reduced pressure The resulting solid was dried overnight in a vacuum oven at 30° C.