Hydrochloric Acid → 2(R)-Amino-5-phenyl-pentanoic acid (2(S)-hydroxy-1(S)-methyl-2-phenyl-ethyl)-methyl-amide

Temperature

-78 °C

A solution of pseudoephedrine glycinamide (1.5 g, 6.75 mmol), prepared and used by the method of Myers et al. (J. Am. Chem. Soc. 1997, 119, 656), and LiCI (1.71 g, 40.5 mmol) in THF (30 mL) was cooled to −78° C. and n-BuLi was added (13.16 mmol, 5.25 mL of a 2.5 M solution). After stirring for 20 min at −78° C., the reaction was warmed to 0° C. and stirred an additional 20 minutes. 3-Phenyl-1-bromopropane (1.3 mL, 7.42 mmol) was added and the reaction was stirred for 2 h at 0° C. Aqueous 1 N HCl (50 mL) and EtOAc (50 mL) were added, the organic phase was separated and extracted with 1 N HCl (50 mL). The aqueous extracts were combined, cooled in an ice bath and slowly basified to pH 14 with 6 N NaOH. The product was extracted with CH2Cl2 (4×50 mL) and the combined extracts were dried over MgSO4 and concentrated to give a yellow oil. Purification by flash chromatography (SiO2 gel, 92:4:4, CH2Cl2:MeOH:triethylamine) delivered 400 mg (78%) of the Product of Example 199, Step A: +APcI MS (M+1)+ 341; 1H NMR=400 MHz (CDCl3) δ: 7.38 (m, 10H), 5.26 (m, 1H), 4.15 (m, 1H), 3.86 (m, 1H), 2.36 (s, 3H).

1. temperaturethe reaction was warmed to 0° C.
2. stirringstirred an additional 20 minutes
3. stirringthe reaction was stirred for 2 h at 0° C
4. customthe organic phase was separated
5. extractionextracted with 1 N HCl (50 mL)
6. temperaturecooled in an ice bath and slowly basified to pH 14 with 6 N NaOH
7. extractionThe product was extracted with CH2Cl2 (4×50 mL)
8. dry with materialthe combined extracts were dried over MgSO4
9. concentrationconcentrated
10. customto give a yellow oil
11. customPurification by flash chromatography (SiO2 gel, 92:4:4, CH2Cl2:MeOH:triethylamine)

ORD record

ord-8abe27118ac34dfc9639b44f66e92981

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06953791B2