Reaktion #161909

Reaktionsgleichung

bromoacetaldehyde diethyl acetal

#13

tert-butyl [(2S)-1-amino-3-phenyl-1-thioxopropan-2-yl]carbamate

→

#14

Ausbeute 10.2%

tert-butyl [(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]carbamate

Ausbeute 10.2%

Lösungsmittel

dioxane

acetone

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed with nitrogen three times
2. 2
   Temperaturbefore being heated to reflux
3. 3
   Einengenconcentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate
5. 5
   Waschenwashed with saturated aqueous sodium bicarbonate solution
6. 6
   Waschenwashed with brine
7. 7
   TrocknenThe organic layer was dried over sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated in vacuo
10. 10
    workup.ADDITIONThe resulting crude orange oil was diluted with ethyl acetate
11. 11
    Einengenbefore being concentrated in vacuo onto silica
12. 12
    Sonstigepurified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane)

Vorschrift

To a mixture of #13 (5.65 g, 20.2 mmol, 1 eq.) in acetone (101 mL, 0.2 M) was added bromoacetaldehyde diethyl acetal (8.76 mL, 58.2 mmol, 2.89 eq.) and 2 drops of 4 M hydrochloric acid in dioxane. The mixture was degassed with nitrogen three times before being heated to reflux. After 2 hours, the reaction was cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and washed with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude orange oil was diluted with ethyl acetate before being concentrated in vacuo onto silica and purified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane) and then by reverse phase chromatography (Method A) to give #14 (625 mg, 10%); HPLC (Protocol E): m/z 304.5 [M+H+], 248.9 [(M−2-methylprop-1-ene)+H+], retention time=7.416 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, major rotamer: δ 7.75 (d, J=3.3 Hz, 1H), 7.75 (br d, J=8.6 Hz, 1H), 7.61 (br d, J=3.1 Hz, 1H), 7.25-7.30 (m, 5H), 4.99 (ddd, J=10.5, 8.9, 4.5 Hz, 1H), 3.29-3.36 (m, 1H, assumed; partially obscured by water signal), 2.98 (dd, J=13.8, 10.6 Hz, 1H), 1.31 (s, 9H).

Quelle