2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone

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

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

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

Procedure: A solution of (−)-B-chlorodiisopinocampheylborane [(−)-DIP-Chloride™] (2.10 g, 6.55 mmoles) in toluene (7 ml) is cooled to 0° C. under nitrogen atmosphere. On the magnetically stirred solution is added in 3 hours a solution of 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone (1.0 g, 4.373 mmoles) in toluene (3 ml). At the end of the addition, the mixture is stirred at 0° C. for further 20 hours. On the reaction mixture is added acetone (0.5 g), followed by a 10% w/w (5 ml) aqueous solution of sodium carbonate, and then demi water (5 ml). The reactive mixture is heated to 20° C. at the end of the additions and transferred in a separator funnel. The mixture is diluted with demi water (5 ml) and toluene (5 ml) and phases are separated. The organic layer is then washed with additional demi water (15 ml) and concentrated and anhydrified under vacuum to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (98% de via GC). The product is purified by chromatography on silica using a toluene:ethyl acetate 9.5:0.5 eluting mixture. After separation, the product (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol is isolated as a colorless oil (0.31 g, 31%). At the end of the addition The reactive mixture is heated to 20° C. at the end of the additions transferred in a separator funnel are separated The organic layer is then washed with additional demi water (15 ml) concentrated to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (98% de via GC) The product is purified by chromatography on silica using a toluene:ethyl acetate 9.5:0.5 eluting mixture After separation

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

Procedure: A solution of (+)-B-chlorodiisopinocampheylborane [(+)-DIP-Chloride™] (2.10 g, 6.55 mmoles) in toluene (7 ml) is cooled to 0° C. under nitrogen atmosphere. On the magnetically stirred solution is added in 3 hours a solution of 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone (1.0 g, 4.373 mmoles) in toluene (3 ml). At the end of the addition, the mixture is stirred at 0° C. for further 20 hours. On the reaction mixture is added acetone (0.5 g), followed by a 10% w/w (5 ml) aqueous solution of sodium carbonate, and then demi water (5 ml). The reactive mixture is heated to 20° C. at the end of the additions and transferred in a separator funnel. The mixture is diluted with demi water (5 ml) and toluene (5 ml) and phases are separated. The organic layer is then washed with additional demi water (15 ml) and concentrated and anhydrified under vacuum to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (99% de via GC). The product is purified by chromatography on silica using a toluene:ethyl acetate 9:1 eluting mixture. After separation, the product (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol is isolated as a colorless oil (0.64 g, 63%). At the end of the addition The reactive mixture is heated to 20° C. at the end of the additions transferred in a separator funnel are separated The organic layer is then washed with additional demi water (15 ml) concentrated to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (99% de via GC) The product is purified by chromatography on silica using a toluene:ethyl acetate 9:1 eluting mixture After separation

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

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

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

Procedure: A solution under stirring of 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone (0.33 g, 1.28 mmol, 88.4 A %) in ethanol (2.5 ml) was cooled to 0° C. under nitrogen. NaBH4 (60.1 mg, 1.59 mmol) was added to the solution and the reaction mixture stirred for 2 hours. After checking that the starting product had disappeared by GC, the mixture was diluted with demi water (7 ml) and dichloromethane (7 ml) and the phases separated. The organic stratum was dried under anhydrous sodium sulphate, filtered and concentrated under vacuum to give raw 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl) ethanol as a mixture of diastereoisomers 54:46 (0.30 g, 70% yield, 67.9 A %). the phases separated The organic stratum was dried under anhydrous sodium sulphate filtered concentrated under vacuum

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

Procedure: A solution of (−)-B-chlorodiisopinocampheylborane [(−)-DIP-Chloride™] (2.10 g, 6.55 mmoles) in toluene (7 ml) is cooled to 0° C. under nitrogen atmosphere. On the magnetically stirred solution is added in 3 hours a solution of 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone (1.0 g, 4.373 mmoles) in toluene (3 ml). At the end of the addition, the mixture is stirred at 0° C. for further 20 hours. On the reaction mixture is added acetone (0.5 g), followed by a 10% w/w (5 ml) aqueous solution of sodium carbonate, and then demi water (5 ml). The reactive mixture is heated to 20° C. at the end of the additions and transferred in a separator funnel. The mixture is diluted with demi water (5 ml) and toluene (5 ml) and phases are separated. The organic layer is then washed with additional demi water (15 ml) and concentrated and anhydrified under vacuum to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (98% de via GC). The product is purified by chromatography on silica using a toluene:ethyl acetate 9.5:0.5 eluting mixture. After separation, the product (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol is isolated as a colorless oil (0.31 g, 31%). At the end of the addition The reactive mixture is heated to 20° C. at the end of the additions transferred in a separator funnel are separated The organic layer is then washed with additional demi water (15 ml) concentrated to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (98% de via GC) The product is purified by chromatography on silica using a toluene:ethyl acetate 9.5:0.5 eluting mixture After separation

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

Procedure: A solution of (+)-B-chlorodiisopinocampheylborane [(+)-DIP-Chloride™] (2.10 g, 6.55 mmoles) in toluene (7 ml) is cooled to 0° C. under nitrogen atmosphere. On the magnetically stirred solution is added in 3 hours a solution of 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone (1.0 g, 4.373 mmoles) in toluene (3 ml). At the end of the addition, the mixture is stirred at 0° C. for further 20 hours. On the reaction mixture is added acetone (0.5 g), followed by a 10% w/w (5 ml) aqueous solution of sodium carbonate, and then demi water (5 ml). The reactive mixture is heated to 20° C. at the end of the additions and transferred in a separator funnel. The mixture is diluted with demi water (5 ml) and toluene (5 ml) and phases are separated. The organic layer is then washed with additional demi water (15 ml) and concentrated and anhydrified under vacuum to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (99% de via GC). The product is purified by chromatography on silica using a toluene:ethyl acetate 9:1 eluting mixture. After separation, the product (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol is isolated as a colorless oil (0.64 g, 63%). At the end of the addition The reactive mixture is heated to 20° C. at the end of the additions transferred in a separator funnel are separated The organic layer is then washed with additional demi water (15 ml) concentrated to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (99% de via GC) The product is purified by chromatography on silica using a toluene:ethyl acetate 9:1 eluting mixture After separation