Trifluoroacetic acid → (R)-2-Amino-3-((tert-butyldiphenylsilyl)oxy)propan-1-ol

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Reaction Conditions

Reaction Steps

To a 2 L three neck flask fitted with a thermometer, mechanical stirrer, under argon was added 4 (46 g, 0.089 mol) and CH2Cl2 (1 L). The clear colorless solution was cooled to 0° C. with an ice/methanol bath. The TFA (132 g, 1.16 mol) was added in one portion. After stirring for 3 hr 30 min and allowing to warm to 20° C., the reaction was complete by HPLC. The reddish brown solution was concentrated under reduced pressure. Toluene (1×100 mL and 1×50 mL) was added to the residue and twice concentrated to remove excess TFA. To the resulting red oil was added methanol (600 mL) and water (200 mL). Potassium carbonate (110 g) was added to the resulting solution and stirred vigorously for 2 hr and 15 min. Dichloromethane (1.2 L) was added to the stirring solution. The aqueous layer was separated and extracted with CH2Cl2 (1 L). The organic layers were combined and dried over MgSO4 (20 g), filtered and concentrated under reduced pressure to 44 g of a cloudy orange oil. The oil was dissolved in CH2Cl2 (200 mL) and dried again over MgSO4 (6 g), filtered and concentrated under reduced pressure to 39 g of product 5 as an orange oil. HPLC analysis showed a purity of 54% at a retention time of 2.8 min at 215 nm (Hewlett Packard series 1100 HPLC instrument, using an Alltech Alltima column (C18, 5μ, 250×4.6 mm), with a flow rate of 1.0 mL/min at 40° C., conditions 0:5:95; Water:Al:MeOH, Al consists of 700 mL of water, 300 mL of methanol, and 3 mL of triethylamine adjusted to pH 3.4 with phosphoric acid). There were three major impurities by HPLC at retention times of 3.1 min (21%), 3.4 min (15%) and 3.8 min (9%). The product 5 was carried on without further purification 1H NMR (60 MHz, CDCl3) δ 7.0-7.7 (m, 10H), 3.4-3.9 (m, 5H), 1.8-2.2 (br s, 1H), 1.1 (s, 9H).

Provenance & Evidence