(2S)-3-(dibenzylamino)-2-fluoropropan-1-ol

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium borohydride (17.7 g, 0.81 mol) was suspended in THF (400 mL) under a nitrogen atmosphere and cooled to −15° C. with stirring. Methyl (2S)-3-(dibenzylamino)-2-fluoropropanoate (188.3 g, 0.62 mol) was suspended in THF (400 mL) and added dropwise to the mixture. On completion of addition, the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 3 h. TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to 0° C. and cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL). Additional water (400 mL) was added then the reaction mixture was extracted with ethyl acetate and the organic phase was concentrated under reduced pressure. The crude residue was dissolved in 2 N hydrochloric acid and the aqueous phase was washed twice with ether. The aqueous phase was basified (pH=10 approx.) with 80% ammonium hydroxide in brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford (2S)-3-(dibenzylamino)-2-fluoro-1-propanol (156.6 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.15–7.38 (m, 10H), 4.65–4.78 (m, 0.5H), 4.48–4.58 (m, 0.5H), 3.50–3.82 (m, 6H), 2.70–2.88 (m, 2H). added dropwise to the mixture On completion of addition to warm to room temperature stirred at this temperature for 3 h consumption of starting material The reaction mixture was cooled to 0° C. cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL) Additional water (400 mL) was added the reaction mixture was extracted with ethyl acetate the organic phase was concentrated under reduced pressure The crude residue was dissolved in 2 N hydrochloric acid the aqueous phase was washed twice with ether extracted with ethyl acetate dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium borohydride (17.7 g, 0.81 mol) was suspended in THF (400 mL) under a nitrogen atmosphere and cooled to −15° C. with stirring. Methyl (2S)-3-(dibenzylamino)-2-fluoropropanoate (188.3 g, 0.62 mol) was suspended in THF (400 mL) and added dropwise to the mixture. On completion of addition, the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 3 h. TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to 0° C. and cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL). Additional water (400 mL) was added then the reaction mixture was extracted with ethyl acetate and the organic phase was concentrated under reduced pressure. The crude residue was dissolved in 2 N hydrochloric acid and the aqueous phase was washed twice with ether. The aqueous phase was basified (pH=10 approx.) with 80% ammonium hydroxide in brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford (2S)-3-(dibenzylamino)-2-fluoro-1-propanol (156.6 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.15-7.38 (m, 10H), 4.65-4.78 (m, 0.5H), 4.48-4.58 (m, 0.5H), 3.50-3.82 (m, 6H), 2.70-2.88 (m, 2H). added dropwise to the mixture On completion of addition to warm to room temperature stirred at this temperature for 3 h consumption of starting material The reaction mixture was cooled to 0° C. cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL) Additional water (400 mL) was added the reaction mixture was extracted with ethyl acetate the organic phase was concentrated under reduced pressure The crude residue was dissolved in 2 N hydrochloric acid the aqueous phase was washed twice with ether extracted with ethyl acetate dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium borohydride (17.7 g, 0.81 mol) was suspended in THF (400 mL) under a nitrogen atmosphere and cooled to −15° C. with stirring. Methyl (2S)-3-(dibenzylamino)-2-fluoropropanoate (188.3 g, 0.62 mol) was suspended in THF (400 mL) and added dropwise to the mixture. On completion of addition, the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 3 h. TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to 0° C. and cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL). Additional water (400 mL) was added then the reaction mixture was extracted with ethyl acetate and the organic phase was concentrated under reduced pressure. The crude residue was dissolved in 2 N hydrochloric acid and the aqueous phase was washed twice with ether. The aqueous phase was basified (pH=10 approx.) with 80% ammonium hydroxide in brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford (2S)-3-(dibenzylamino)-2-fluoro-1-propanol (156.6 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ7.15-7.38 (m, 10H), 4.65-4.78 (m, 0.5H), 4.48-4.58 (m, 0.5H), 3.50-3.82 (m, 6H), 2.70-2.88 (m, 2H). added dropwise to the mixture On completion of addition to warm to room temperature stirred at this temperature for 3 h consumption of starting material The reaction mixture was cooled to 0° C. cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL) Additional water (400 mL) was added the reaction mixture was extracted with ethyl acetate the organic phase was concentrated under reduced pressure The crude residue was dissolved in 2 N hydrochloric acid the aqueous phase was washed twice with ether extracted with ethyl acetate dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium borohydride (17.7 g, 0.81 mol) was suspended in THF (400 mL) under a nitrogen atmosphere and cooled to −15° C. with stirring. Methyl (2S)-3-(dibenzylamino)-2-fluoropropanoate (188.3 g, 0.62 mol) was suspended in THF (400 mL) and added dropwise to the mixture. On completion of addition, the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 3 h. TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to 0° C. and cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL). Additional water (400 mL) was added then the reaction mixture was extracted with ethyl acetate and the organic phase was concentrated under reduced pressure. The crude residue was dissolved in 2 N hydrochloric acid and the aqueous phase was washed twice with ether. The aqueous phase was basified (pH=10 approx.) with 80% ammonium hydroxide in brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford (2S)-3-(dibenzylamino)-2-fluoro-1-propanol (156.6 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ7.15-7.38 (m, 10H), 4.65-4.78 (m, 0.5H), 4.48-4.58 (m, 0.5H), 3.50-3.82 (m, 6H), 2.70-2.88 (m, 2H). added dropwise to the mixture On completion of addition to warm to room temperature stirred at this temperature for 3 h consumption of starting material The reaction mixture was cooled to 0° C. cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL) Additional water (400 mL) was added the reaction mixture was extracted with ethyl acetate the organic phase was concentrated under reduced pressure The crude residue was dissolved in 2 N hydrochloric acid the aqueous phase was washed twice with ether extracted with ethyl acetate dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium borohydride (17.7 g, 0.81 mol) was suspended in THF (400 mL) under a nitrogen atmosphere and cooled to −15° C. with stirring. Methyl (2S)-3-(dibenzylamino)-2-fluoropropanoate (188.3 g, 0.62 mol) was suspended in THF (400 mL) and added dropwise to the mixture. On completion of addition, the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 3 h. TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to 0° C. and cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL). Additional water (400 mL) was added then the reaction mixture was extracted with ethyl acetate and the organic phase was concentrated under reduced pressure. The crude residue was dissolved in 2 N hydrochloric acid and the aqueous phase was washed twice with ether. The aqueous phase was basified (pH=10 approx.) with 80% ammonium hydroxide in brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford (2S)-3-(dibenzylamino)-2-fluoro-1-propanol (156.6 g, 92%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.15-7.38 (m, 10H), 4.65-4.78 (m, 0.5H), 4.48-4.58 (m, 0.5H), 3.50-3.82 (m, 6H), 2.70-2.88 (m, 2H). added dropwise to the mixture On completion of addition to warm to room temperature stirred at this temperature for 3 h consumption of starting material The reaction mixture was cooled to 0° C. cautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL) Additional water (400 mL) was added the reaction mixture was extracted with ethyl acetate the organic phase was concentrated under reduced pressure The crude residue was dissolved in 2 N hydrochloric acid the aqueous phase was washed twice with ether extracted with ethyl acetate dried over anhydrous sodium sulfate filtered concentrated under reduced pressure