Reaction #1458422

Reaction equation

benzyl O-(diphenyloxyphosphoryl)-DL-homoserinate

(R)3-dodecanoyloxytetradecanoic acid

N-methylmorpholin

isobutyl chloroformate

→

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

Solvents

water

tetrahydrofurane

triethylamine

tetrahydrofurane

Conditions

Workup

1. 1
   workup.STIRRINGAfter stirring overnight at room temperature
2. 2
   workup.ADDITIONwere added to the residue
3. 3
   ExtractionThe mixture was then extracted with ethyl acetate (2×30 ml)
4. 4
   Washwashed in succession with water (20 ml) and brine (20 ml)
5. 5
   Dryingdried over magnesium sulfate
6. 6
   OtherThe solvent was evaporated
7. 7
   Otherthe residue was purified by flash chromatography (hexane-ethyl acetate 2:1, Rf=0.29)

Procedure

4.284 g (10.07 mmol) of (R)3-dodecanoyloxytetradecanoic acid prepared acccording to the method disclosed in Bull. Chem. Soc. Jpn., 60 (1987), 2205–2214, were dissolved in 30 ml of tetrahydrofurane and the solution was cooled down to −15° C. in an ice-cold brine bath. 1,108 ml (10.07 mmol) of N-methylmorpholin and 1.31 ml (10.07 mmol) of isobutyl chloroformate were then added. Stirring was continued for 30 minutes. To the reaction mixture, there was added 5.724 g (10.07 mmol) of benzyl O-(diphenyloxyphosphoryl)-DL-homoserinate in a mixture of 30 ml of tetrahydrofurane and 5 ml of triethylamine. After stirring overnight at room temperature, the solvent was driven away under vacuum and 20 ml of water were added to the residue. The mixture was 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 magnesium sulfate. The solvent was evaporated and the residue was purified by flash chromatography (hexane-ethyl acetate 2:1, Rf=0.29); yield 7.455 g i.e 87.1% 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, 24.47, 13.91.

Source