Реакция #161909

Уравнение реакции

bromoacetaldehyde diethyl acetal

#13

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

→

#14

Выход 10.2%

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

Выход 10.2%

Растворители

dioxane

acetone

Условия реакции

Обработка

1. 1
   ДругоеThe mixture was degassed with nitrogen three times
2. 2
   Температураbefore being heated to reflux
3. 3
   Концентрированиеconcentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate
5. 5
   Промывкаwashed with saturated aqueous sodium bicarbonate solution
6. 6
   Промывкаwashed with brine
7. 7
   СушкаThe organic layer was dried over sodium sulfate
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated in vacuo
10. 10
    workup.ADDITIONThe resulting crude orange oil was diluted with ethyl acetate
11. 11
    Концентрированиеbefore being concentrated in vacuo onto silica
12. 12
    Другоеpurified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane)

Методика

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).

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