1-Hydroxybenzotriazole → Artelinate

HRID 990587

Reaktionsgleichung

Reaktionsgleichung von HRID 990587
[CH3:1][C@@H:2]1[C@H:11]2[CH2:12][CH2:13][C@@:14]3([CH3:18])[O:16][O:17][C@@:10]42[C@H:5]([C@H:6]([CH3:30])[C@H:7]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]([OH:29])=[O:28])=[CH:25][CH:26]=2)[O:8][C@@H:9]4[O:15]3)[CH2:4][CH2:3]1.ON1C2C=CC=CC=2N=N1>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:1][C@H:2]1[C@@H:11]2[CH2:12][CH2:13][C:14]3([CH3:18])[O:16][O:17][C@:10]42[C@H:5]([C@@H:6]([CH3:30])[C@@H:7]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]([OH:29])=[O:28])=[CH:23][CH:22]=2)[O:8][C@@H:9]4[O:15]3)[CH2:4][CH2:3]1

Komponenten

5

Edukt 2

HCID 757711-HydroxybenzotriazoleHCID 717190354-[[(1R,4R,5S,8S,9S,10R,12R,13S)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzoic acid

Produkt 1

HCID 73156ArtelinateAusbeute 119,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6212ChloroformLösungsmittel

Versuchsvorschrift

8 arm PEG (20 Kda) (2.0 g, ˜0.10 mmol) was dissolved in CHCl3 (300 ml) and the solvent was removed in vacuo. The gum was dissolved in CH2Cl2 (˜30 ml) under an argon atmosphere and to the solution was added artelinic acid (0.85 g, 2.00 mmol), 1-hydroxybenzotriazole (0.085 g, 0.63 mmol) and 4-(dimethylamino)pyridine (cat.). The mixture was allowed to reflux overnight under an argon atmosphere. The cloudy mixture was concentrated to dryness and to the residue was added CH2Cl2 (˜5 ml). To the slightly turbid solution was added EtOH (˜100 ml) and a white solid was obtained upon cooling in an ice bath for ˜3 h. Repeating the purification afforded pure 8 arm PEG (20 Kda) artelinate (1.00 g) as a water-soluble white solid. 1H NMR (CDCl3, 300 MHz) indicated a near quantitative conversion. HPLC (C-4 reversed-phase) indicated a mixture of products arising from different degrees of substitution. Partial 1H NMR data (CDCl3, 300 MHz): δ 0.94 (s, 24H, C9—CH3), 0.95 (s, 24H, C6—CH3), 1.44 (s, 24H, C3—CH3), 2.68 (m, 8H, H-9), 3.63 (bs, 1818H, PEG backbone), 4.45 (t, 16H, J 4.4 Hz, PEG—OCH2CH2O—COAr), 4.56 (d, 8H, J 13.1 Hz, OCHAHB—Ar), 4.91-4.96 (m, 16H, H-10 overlapped with OCHAHB—Ar), 5.44 (s, 7.5H, H-12), 7.37 (d, 8H, J 7.8 Hz, Ar), 8.01 (d, 8H, Ar).

Aufarbeitung

  1. customthe solvent was removed in vacuo
  2. dissolutionThe gum was dissolved in CH2Cl2 (˜30 ml) under an argon atmosphere and to the solution
  3. temperatureto reflux overnight under an argon atmosphere
  4. concentrationThe cloudy mixture was concentrated to dryness and to the residue
  5. additionwas added CH2Cl2 (˜5 ml)
  6. additionTo the slightly turbid solution was added EtOH (˜100 ml)
  7. customa white solid was obtained
  8. temperatureupon cooling in an ice bath for ˜3 h
  9. customRepeating the purification

Quellen und Nachweise

ORD-Eintrag
ord-d7625b3c47fd42269761d3b55989bd9a
Quelldatensatz
uspto-grants-2002_10
Patentnummer
US06461603B2

Verknüpfte Notizen

Wird geladen…