Reacción #1801931

Ecuación de reacción

(R)-3-dodecanoyloxytetradecanoic acid

N-methylmorpholin

isobutyl chloroformate

benzyl O-(diphenyloxyphosphoryl)-DL-homoserinate

→

Benzyl 2-[(R)-3-Dodecanoyloxytetradecanoylamino]-4-(diphenyloxyphosphoryloxy)butanoate

Disolventes

H2O

THF Et3N

tetrahydrofurane THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGAfter stirring for 18 hours at room temperature
2. 2
   Extracciónextracted with ethyl acetate (2×30 ml)
3. 3
   Lavadowashed in succession with water (20 ml) and brine (20 ml)
4. 4
   Secadodried over MgSO4
5. 5
   Otrobefore evaporating the solvent
6. 6
   Otroflash chromatography purification on a silica gel (2/1 hexane/ethyl acetate eluent)
7. 7
   Otrothe required benzyl ester was recovered (7.455 g 87%) as a cristalline solid

Procedimiento

(R)-3-dodecanoyloxytetradecanoic acid (4.284 g; 10.07 mmol, 1 eq.) prepared according to the method disclosed in [Bull. Chem. Soc. Jpn., 60 (1987), 2205-2214], was dissolved in tetrahydrofurane THF (30 ml) and the solution was cooled down to −15° C. N-methylmorpholin (1.108 ml; 10.07 mmol, 1 eq.) and isobutyl chloroformate (1.31 ml; 10.07 mmol; 1 eq.) were then added. The reaction mixture was kept under stirring for 30 minutes at −15° C. To the reaction mixture, there was next added benzyl O-(diphenyloxyphosphoryl)-DL-homoserinate (5.724 g; 10.07 mmol 1 eq.) in a THF/Et3N mixture (30 ml/5 ml). After stirring for 18 hours at room temperature, the solvent was driven away under vacuum. The residue was diluted with H2O (20 ml) and then extracted with ethyl acetate (2×30 ml). The organic layers were pooled, washed in succession with water (20 ml) and brine (20 ml) and dried over MgSO4 before evaporating the solvent. By running flash chromatography purification on a silica gel (2/1 hexane/ethyl acetate eluent), the required benzyl ester was recovered (7.455 g 87%) as a cristalline solid. m.p.=31.0°-32.1° C., 1H-NMR (CDCl3, 250 MHz), δ in ppm: 7.4-7.1 (m, 15H), 6.90 (2d, 1H, 3J=7.6 Hz, NH), 5.3-5.1 (m, 3H), 4.7 (m, 1H), 4.35 (m, 2H), 2.45 (m, 2H), 2.4-2.1 (m, 4H), 1.6 (m, 4H), 1.4-1.1 (m, 34H), 0.9 (t, 6H). 13C-NMR (CDCl3, 63 MHz), δ in ppm: 173.01, 171.08, 169.66, 150.18, (d, 2JP,C=7.1 Hz), 135.01, 129.60, 128.33, 128.14, 127.96, 125.21, 119.80 (d, 3JP,C=5.0 Hz), 70.69, 67.05, 65.19 (d, 2JP,C=5.6 Hz), 49.13, 40.97, 40.77 (2 diast.), 34.20, 33.98, 33.82, 31.70, 29.42, 29.34, 29.14, 28.94, 25.01, 24.77, 22.47, 13.91.

Fuente