Reaktion #832646

Reaktionsgleichung

(S)-3-t-butoxycarbonylamino-(R)-2-hydroxy-4-cyclohexylbutyric acid methyl ester

benzyl bromide

benzyl ether

hydrochloric acid

Sodium hydride

→

(S)-3-t-butoxycarbonylamino-(R)-2-benzyloxy-4-cyclohexylbutyric acid methyl ester

Lösungsmittel

dimethylformamide

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to 25° C. over a period of about 15 minutes
2. 2
   Temperaturcooled
3. 3
   SonstigeThe ether layer was separated
4. 4
   Extraktionthe aqueous layer was extracted thoroughly with ether
5. 5
   Waschenwashed with 1M lithium chloride solution (2×30 ml.)
6. 6
   Trocknendried over magnesium sulfate
7. 7
   SonstigeThe concentrate was chromatographed on silica (0.032-0.064 mm) in 1:6 ether-hexane
8. 8
   Einengenconcentrated
9. 9
   Sonstigerechromatographed on 50 g
10. 10
    Waschensilica, eluting with 1:10 ether-hexane
11. 11
    Einengenconcentrated
12. 12
    Sonstigegave 6.45 g

Vorschrift

(S)-3-t-butoxycarbonylamino-(R)-2-hydroxy-4-cyclohexylbutyric acid methyl ester (4.58 g., 14.52 mmol) was dissolved in anhydrous dimethylformamide (30 ml.) together with benzyl bromide (2.6 ml., 21.7 mmol) and cooled to 0° C. Sodium hydride (freed of oil by washing with hexane, 450 mg., 19.6 mmol) was added in one portion and the mixture was stirred under nitrogen and allowed to warm to 25° C. over a period of about 15 minutes. The mixture was poured slowly into a stirred ice-cooled mixture of ether (500 ml.) and excess aqueous 1N hydrochloric acid, and was then combined with two previous reaction mixtures where a total of 4.27 mmol (1.34 g.) of this hydroxy methyl ester had been etherified and worked up in an identical fashion. The ether layer was separated and the aqueous layer was extracted thoroughly with ether. The ether layers were combined and washed with 1M lithium chloride solution (2×30 ml.), and dried over magnesium sulfate. The concentrate was chromatographed on silica (0.032-0.064 mm) in 1:6 ether-hexane. Several impure fractions were combined, concentrated, and rechromatographed on 50 g. silica, eluting with 1:10 ether-hexane. The pure fractions combined and concentrated gave 6.45 g. (85%) of the benzyl ether.

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