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

HRID 1371240Notes

Reaction equation

HRID 1371240 reaction equation
[C:1]([O:14][C@H:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:16][C:17]([OH:19])=O)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].CN1CCOCC1.ClC(OCC(C)C)=O.[C:46]1([O:52][P:53]([O:62][CH2:63][CH2:64][CH:65]([C:67]([O:69][CH2:70][C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)=[O:68])[NH2:66])([O:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)=[O:54])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>O1CCCC1.C(N(CC)CC)C.O>[C:1]([O:14][C@H:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:16][C:17]([NH:66][CH:65]([CH2:64][CH2:63][O:62][P:53]([O:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)([O:52][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:54])[C:67]([O:69][CH2:70][C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1)=[O:68])=[O:19])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1246803-Dodecanoyltetradecanoic acidHCID 11362711benzyl O-(diphenyloxyphosphoryl)-DL-homoserinate

Product 1

HCID 67493901Benzyl 2-[(R)-3-DodecanovIoxytetradecanovlamino]-4-(diphenyloxyphosphoryloxy)butanoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-15 °C

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.

Workup

  1. stirringAfter stirring overnight at room temperature
  2. additionwere added to the residue
  3. extractionThe mixture was then extracted with ethyl acetate (2×30 ml)
  4. washwashed in succession with water (20 ml) and brine (20 ml)
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified by flash chromatography (hexane-ethyl acetate 2:1, Rf=0.29)

Sources & evidence

ORD record
ord-fbf74e49d6e84ccf9c5b0d3bf2d219de
Source dataset
uspto-grants-2007_01
Patent number
US07157092B1

Reaction notes

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