تفاعل #58684

معادلة التفاعل

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

المردود 95.8%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction was cooled
2. 2
   أخرىquenched with saturated NH4Cl
3. 3
   أخرىThe layers were separated
4. 4
   استخلاصthe aqueous layer was extracted three times with 20 ml of EtOAc
5. 5
   تجفيفThe organic phase was dried over Na2SO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated under reduced pressure
8. 8
   أخرىThe oil was purified by silica chromatography

الإجراء التجريبي

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).

المصدر