Lithium borohydride → HCID 9943424, compound

Temperature

-15 °C

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).

1. additionadded dropwise to the mixture
2. additionOn completion of addition
3. temperatureto warm to room temperature
4. stirringstirred at this temperature for 3 h
5. customconsumption of starting material
6. temperatureThe reaction mixture was cooled to 0° C.
7. customcautiously quenched with a saturated aqueous solution of ammonium chloride (300 mL)
8. additionAdditional water (400 mL) was added
9. extractionthe reaction mixture was extracted with ethyl acetate
10. concentrationthe organic phase was concentrated under reduced pressure
11. dissolutionThe crude residue was dissolved in 2 N hydrochloric acid
12. washthe aqueous phase was washed twice with ether
13. extractionextracted with ethyl acetate
14. dry with materialdried over anhydrous sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated under reduced pressure

ORD record

ord-c59ceebc2edd4e9eb0f9fa5cdd144a8e

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07034176B2