Reaktion #53956

Reaktionsgleichung

tert-butyl 2-(dibenzylamino)-propanoate

(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehyde

tert-butyl bromoacetate

dibenzylamine

lithium diisopropylamide

→

tert-Butyl 2-(dibenzylamino)-propanoate

tert-butyl (2S,3S)-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-2-(dibenzylamino)-3-hydroxypropanoate

Ausbeute 14.4%

Lösungsmittel

ethanol

tetrahydrofuran

tetrahydrofuran

1,4-dioxane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe resulting mixture was stirred at −30° C. for 15 h under argon
2. 2
   WaschenThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
3. 3
   Trocknendried over magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated to dryness in vacuo
6. 6
   SonstigeThe residue was chromatographed (flash column, silica gel, methylene chloride:n-hexane:methanol:diethyl ether=49:49:1:1)

Vorschrift

tert-Butyl 2-(dibenzylamino)-propanoate was prepared from tert-butyl bromoacetate (10 ml, 68 mmole) and dibenzylamine (26.5 ml, 138 mmole) in 1,4-dioxane (20 ml) and abs. ethanol (25 ml), following the literature procedure (Scolastico, C. Tetrahedron Letts., 1987, 43, 2317). A solution of tert-butyl 2-(dibenzylamino)-propanoate (4.75 g, 15.23 mmole) in anhydrous tetrahydrofuran (60 ml) was cooled at −78° C. under argon. A solution of lithium diisopropylamide (7.6 ml, 15.23 mmole, 2.0 M solution in tetrahydrofuran, Aldrich) was introduced to this cooled solution over a period of 15 min, and the resulting reddish orange solution was stirred at this temperature for 1 h. A solution of 1-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehyde (4.5 g, 7.62 mmole, obtained from Reference Example 3) in anhydrous tetrahydrofuran was added via syringe to the cooled mixture over a period of 15 min. The resulting mixture was stirred at −30° C. for 15 h under argon, and diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. The residue was chromatographed (flash column, silica gel, methylene chloride:n-hexane:methanol:diethyl ether=49:49:1:1) to give tert-butyl (2S,3S)-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-2-(dibenzylamino)-3-hydroxypropanoate (990 mg, 14.4%) as a white amorphous solid.

Quelle