Reacción #438659

Ecuación de reacción

NaHMDS

trimethyl phosphonoacetate

M-BOC

1,3-Dibenzyl-4-hydroxyimino-piperidine-3-carboxylic acid methyl ester

3-benzyl-3-formyl-piperazine-1-carboxylic acid tert-butyl ester

compound

3-(2,4-Difluoro-Benzyl)-3-Formyl-Piperazine-1-Carboxylic Acid Tert-Butyl Ester

M-tBu

1,3-Dibenzyl-4-hydroxyimino-piperidine-3-carboxylic acid methyl ester

M-BOC

1,3-Dibenzyl-4-hydroxyimino-piperidine-3-carboxylic acid methyl ester

→

3-Benzyl-3-(2-Methoxycarbonyl-Vinyl)-Piperazine-1-Carboxylic Acid Tert-Butyl Ester

Disolventes

THF

THF

methylene chloride

EtOAc

water

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGAfter stirring for 16 hours
3. 3
   LavadoThe combined extracts were washed with brine
4. 4
   Secadodried (MgSO4)
5. 5
   Concentraciónconcentrated
6. 6
   OtroThe product was then purified by silica gel chromatography
7. 7
   Otro5% MeOH in methylene chloride as eluents to afford a 7:3 E

Procedimiento

To a THF (1 mL) solution of NaHMDS at 0° C. was added trimethyl phosphonoacetate (0.18 mL, 1.1 mmol), dropwise. After stirring for 1 hour, a THF (1 mL) solution of crude 3-benzyl-3-formyl-piperazine-1-carboxylic acid tert-butyl ester (0.34 mg, 0.92 mmol), prepared analogous to the compound of Example 198, Step A, was added and the reaction was allowed to warm to room temperature. After stirring for 16 hours, the product was isolated by extraction from water with EtOAc (2×) and methylene chloride (2×). The combined extracts were washed with brine, dried (MgSO4) and concentrated. The product was then purified by silica gel chromatography using methylene chloride, then 5% MeOH in methylene chloride as eluents to afford a 7:3 E:Z mixture of olefins of the compound of Example 201, Step A (0.38 g, 81%), where the Z isomer had lactamized: +APcl MS (M+1, ester)+ 361, (M-tButyl+1, ester)+ 305, (M-tBu+1, lactam)+ 273, (M-BOC+1, ester)+ 261, (M-BOC+1, lactam)+ 229; 1H NMR (400 MHz, CDCl3) δ: 7.30-7.05 (arom, series of m, 5 H), 6.91 (lactam olefin, d, 0.3H), 6.75 (ester olefin, d, 0.7H), 6.09 (lactam olefin, d, 0.3H), 5.88 (ester olefin, d, 0.7H), 3.71 (ester Me, s 2.1H), 1.47 (BOC, s, 9H).

Fuente