反应 #58684

反应方程式

Intermediate 53

piperidine-1,3-dicarboxylic acid 1-tert-butyl ester-3-methyl ester

NaHMDS

iodomethane

→

3-methyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

收率 95.8%

溶剂

THF

反应条件

后处理

1. 1
   温度The reaction was cooled
2. 2
   其他quenched with saturated NH4Cl
3. 3
   其他The layers were separated
4. 4
   萃取the aqueous layer was extracted three times with 20 ml of EtOAc
5. 5
   干燥The organic phase was dried over Na2SO4
6. 6
   过滤filtered
7. 7
   浓缩concentrated under reduced pressure
8. 8
   其他The oil was purified by silica chromatography

实验过程

To a −78° C. stirred solution of Intermediate 53 (2.22 g, 9.13 mmol) in dry THF (30 ml) was added NaHMDS (sodium hexamethyldisilazane) (1.0 M in THF, 10.03 mmol) dropwise. The reaction was stirred at this temperature for 30 minutes and then iodomethane (0.682 ml, 10.95 mmol) was added dropwise. The reaction was allowed to warm to room temperature overnight with good stirring. The reaction was cooled and then quenched with saturated NH4Cl. The layers were separated and the aqueous layer was extracted three times with 20 ml of EtOAc and the organic extracts were combined. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The oil was purified by silica chromatography using hexanes/EtOAc (0>15%) to yield 2.25 g (95.8%) of 3-methyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (Intermediate 54). 1H NMR (400 MHz, CDCl3) δ ppm 1.0 (s, 3 H), 1.3 (s, 9 H), 1.4 (m, 2 H), 1.9 (m, 2 H), 3.0 (d, J=13.2 Hz, 1 H), 3.1 (m, 1 H), 3.3 (m, 1 H), 3.5 (s, 3 H), 3.7 (d, J=13.4 Hz, 1 H).

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