Isopropyl Acetate → 2-Amino-1,2-diphenylethanol

Participants

Reaction Conditions

Reaction Steps

α-Bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid (I) (111 g, 362.4 mmol) and (1R,2S)-(−)-2-amino-1,2-diphenylethanol (II) (the chiral amine, 75 g, 351 mmol, Aldrich) and tetrabutylammonium bromide (catalytic nucleophile, 2.4 g) were charged to a flask. I was obtained by/from Aerojet Fine Chemicals (a Division of Gencorp, Rancho Cordova, Calif.). To this was added 3 L of a 1:1 mixture of i-propyl acetate (i-PrOAc) and methyl t-butyl ether (MTBE). The resulting slurry was heated to 55-60° C. for 24 to 48 h. Reaction was deemed complete when the ratio of the diastereomers was ≧94:6 (R:S). The reaction was cooled to room temperature and the diastereomeric salt, (R)-α-bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid, [R-(R*,S*)]-β-amino-α-phenylbenzeneethanol salt (1:1) (IA), was isolated by filtration. The product cake was washed with 850 mL of MTBE. The MTBE wet product cake was suspended in 1800 mL of MTBE. Water, 1800 mL was added. The pH of the aqueous phase was adjusted to between 1 and 2 with methanesulfonic acid (˜23 mL). The phases were separated and the lower aqueous phase was extracted with MTBE (3×1L). The combined organic phases were washed with water (250 mL). The product, (R)-α-bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid (IB)was used directly in the next step without isolation. In process yield and quality was 101.0 g, 93.0 M%, 87.4% ee (enantiomeric excess). IB: 1H NMR (CDCl3): δ(ppm)=4.30 (m, 1H), 3.72 (m, 2H), 2.96 (s, 3 H), 2.48 (m, 1H), 2.27 (m, 1H), 1.39 (s, 6H). 13C NMR (CDCl3): δ (ppm)=176.7, 172.2, 155.2, 61.4, 41.7, 36.6, 33.2, 24.4, 21.9, 21.9. IR (KBr): ν (cm−1)=3000 (br), 1740 (s), 1680 (s), 1450 (br), 1250 (s).

Provenance & Evidence