Isobutane → (S)-2-(tert-butoxycarbonylamino)-3-(3-chloro-4-hydroxyphenyl)propionic acid methyl ester

Temperatur

25 °C

In a 10 mL round-bottomed flask, (S)-2-(tert-butoxycarbonylamino)-3-(3-chloro-4-hydroxyphenyl)propanoate dicyclohexylammonium salt (300 mg, 604 μmol, Eq: 1.00) was combined with dry THF (2 mL) to give a white suspension. LiOH hydrate (38.4 mg, 905 μmol, Eq: 1.50) was added and the mixture was stirred for 30 min at 25° C. Then Me2SO4 (80.1 mg, 60.7 μL, 604 μmol, Eq: 1.00) was added. The reaction mixture was heated to 80° C. and stirred for 2 h. After that the mixture was stirred for 18 h at 50° C. The crude reaction mixture was concentrated in vacuo. The reaction mixture was poured into saturated aqueous NaHCO3 solution and extracted with AcOEt (2×). The organic layers were combined and washed with brine (1×). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 4/1, 3/1) to yield a colorless oil (132 mg; 66%). m/z=330.2 [M+H]+; 274.1 [M+H-tBu]+; 230.2 [M+H-Boc]+.

1. customto give a white suspension
2. temperatureThe reaction mixture was heated to 80° C.
3. stirringstirred for 2 h
4. stirringAfter that the mixture was stirred for 18 h at 50° C
5. customThe crude reaction mixture
6. concentrationwas concentrated in vacuo
7. additionThe reaction mixture was poured into saturated aqueous NaHCO3 solution
8. extractionextracted with AcOEt (2×)
9. washwashed with brine (1×)
10. dry with materialThe organic layers were dried over Na2SO4
11. concentrationconcentrated in vacuo
12. customThe crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 4/1, 3/1)
13. customto yield a colorless oil (132 mg; 66%)

ORD-Eintrag

ord-a08e45cbe89545aa971d8a50477f3ca7

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09290467B2