Trimethylsilylacetylene → 1,1-Dimethylethyl 4-hydroxy-4-[(trimethylsilyl)ethynyl]-1-piperidinecarboxylate

Temperature

-40 °C

To a cooled (-40° C.) solution of trimethylsilylacetylene (34 ml 241 mmol) in anhydrous tetrahydrofuran (400 ml) under an atmosphere of nitrogen was added slowly n-butyl lithium (96 ml of a 2.5. M solution in hexanes, 241 mmol). After addition the mixture was stirred at -40° C. for 1 hour then cooled to -78° C. To this mixture was added via a cannula a solution of 1-tert-butyloxycarbonyl-4-piperidone (40 g, 201 mmol) in anhydrous tetrahydrofuran (250 ml). After addition the mixture was stirred at -78° C. for 1 hour, the cooling bath removed and the mixture stirred at room temperature for 72 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (300 ml), stirred for a further 10 minutes and poured into water (500 ml) and extracted with ethyl acetate (3×300 ml). The combined organic solutions were washed with water (500 ml), brine (300 ml), dried (MgSO4) and evaporated to afford the title compound (55 g, 92%); mp 75° C.; δH (250 MHz, CDCl3) 0.19 (9H, s), 1.48 (9H, s), 1.63-1.74 (2H, m), 1.80-1.92 (2H, m), 3.18-3.28 (2H, m), 3.71-3.84 (2H, m); mlz (ES) 298 (M+ +1).

1. additionAfter addition the mixture
2. temperaturethen cooled to -78° C
3. additionAfter addition the mixture
4. stirringwas stirred at -78° C. for 1 hour
5. customthe cooling bath removed
6. stirringthe mixture stirred at room temperature for 72 hours
7. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride (300 ml)
8. stirringstirred for a further 10 minutes
9. additionpoured into water (500 ml)
10. extractionextracted with ethyl acetate (3×300 ml)
11. washThe combined organic solutions were washed with water (500 ml), brine (300 ml)
12. dry with materialdried (MgSO4)
13. customevaporated

ORD record

ord-4bd16f6510854527929309911c748e27

Source dataset

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06048878