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

HRID 1714749Notes

Reaction equation

HRID 1714749 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.C1COCC1.O.C1COCC1.CCN(CC)CC>[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 22180045THF tetrahydrofuraneSolventHCID 68616177Triethylamine tetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

(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.

Workup

  1. stirringAfter stirring for 18 hours at room temperature
  2. extractionextracted with ethyl acetate (2×30 ml)
  3. washwashed in succession with water (20 ml) and brine (20 ml)
  4. dry with materialdried over MgSO4
  5. custombefore evaporating the solvent
  6. customflash chromatography purification on a silica gel (2/1 hexane/ethyl acetate eluent)
  7. customthe required benzyl ester was recovered (7.455 g 87%) as a cristalline solid

Sources & evidence

ORD record
ord-ed347ad764b84b42858febe342144640
Source dataset
uspto-grants-2010_09
Patent number
US07799762B2

Reaction notes

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