Tetrahydrofuran → (1S)-(4-{[5-tert-butoxycarbonylamino-1-(diethoxyphosphoryloxymethyl)-pentyl]isobutyl-sulfamoyl}-phenyl)-carbamic acid tert-butyl ester

HRID 132695

Reaktionsgleichung

Reaktionsgleichung von HRID 132695
[C:1]([O:5][C:6](=[O:37])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14](=[O:36])(=[O:35])[N:15]([C@H:20]([CH2:33][OH:34])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C1COCC1.[CH2:43]([O:45][P:46](Cl)([O:48][CH2:49][CH3:50])=[O:47])[CH3:44].[H-].[Na+]>C(OP(OCC)(OCC)=O)C>[C:1]([O:5][C:6](=[O:37])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([S:14](=[O:36])(=[O:35])[N:15]([C@H:20]([CH2:33][O:34][P:46]([O:48][CH2:49][CH3:50])([O:45][CH2:43][CH3:44])=[O:47])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:16][CH:17]([CH3:18])[CH3:19])=[CH:12][CH:13]=1)([CH3:3])([CH3:4])[CH3:2]

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 13139Diethyl chlorophosphateHCID 24758Sodium hydrideHCID 59733922(1S)-{4-[(5-tert-butoxycarbonylamino-1-hydroxymethyl-pentyl)-isobutyl-sulfamoyl]-phenyl}-carbamic acid tert-butyl ester

Produkt 1

HCID 59733918(1S)-(4-{[5-tert-butoxycarbonylamino-1-(diethoxyphosphoryloxymethyl)-pentyl]isobutyl-sulfamoyl}-phenyl)-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6535Triethyl PhosphateLösungsmittel

Versuchsvorschrift

2.00 g (3.7 mmol) (1S)-{4-[(5-tert-butoxycarbonylamino-1-hydroxymethyl-pentyl)-isobutyl-sulfamoyl ]-phenyl}-carbamic acid tert-butyl ester (VII) (example 1, step D) is dissolved in 0.63 mL triethylphosphate and 10 mL THF at 0° C. under inert argon atmosphere. 0.63 mL (4.44 mmol) diethylchlorophosphate is added and then 0.25 g (6.2 mmol), NaH 60% in oil is added in portionwise. The mixture is allowed to warm to room temperature and left to stir for 2 h (LC-MS showed completion after 1 h). To the solution is added 2 0 mL of Amberlite XAD-2 resin and the slurry thoroughly mixed and added to 200 mL ice water. After stirring for 15 min. the resin suspension is filtered and the resin washed several times with distilled water (500 mL). The desired product is desorbed from the resin with acetone (5×50 mL), EtOAc (5×50 mL), the organic phase is then dried over Na2SO4. After evaporation of the solvent 2.66 g (89%) of clear oil is obtained. The crude product contains a fraction with two diethyl phosphates and is used as is in the next step.

Aufarbeitung

  1. customat 0° C.
  2. waitleft
  3. additionthe slurry thoroughly mixed
  4. stirringAfter stirring for 15 min. the resin suspension
  5. filtrationis filtered
  6. washthe resin washed several times with distilled water (500 mL)
  7. dry with materialthe organic phase is then dried over Na2SO4
  8. customAfter evaporation of the solvent 2.66 g (89%) of clear oil
  9. customis obtained

Quellen und Nachweise

ORD-Eintrag
ord-a53b81afb64d4688baddce56a827a22d
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388008B2

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