Acetic Acid → HCID 86587952, Verbindung

HRID 25732Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 25732
[CH2:1]([O:8][C:9](=[O:24])[NH:10][CH:11]([C:17](=[O:23])[NH:18][CH2:19][CH2:20][CH:21]=O)[CH:12]([OH:16])[CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][C@H:26]([C@@H:32]([OH:54])[C@H:33]1[C@@H:37]([O:38][C:39](=[O:41])[CH3:40])[C@@H:36]([O:42][C:43](=[O:45])[CH3:44])[C@H:35]([N:46]2[CH:51]=[CH:50][C:49](=[O:52])[NH:48][C:47]2=[O:53])[O:34]1)[C:27]([O:29][CH2:30][CH3:31])=[O:28].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[C:39]([O:38][C@H:37]1[C@@H:36]([O:42][C:43](=[O:45])[CH3:44])[C@H:35]([N:46]2[CH:51]=[CH:50][C:49](=[O:52])[NH:48][C:47]2=[O:53])[O:34][C@@H:33]1[C@H:32]([OH:54])[CH:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[NH:25][CH2:21][CH2:20][CH2:19][NH:18][C:17](=[O:23])[C@H:11]([C@@H:12]([OH:16])[CH:13]([CH3:15])[CH3:14])[NH:10][C:9](=[O:24])[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:41])[CH3:40]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 20759880HCID 20759880, VerbindungHCID 86587948ethyl (2R,3R)-2-amino-3-hydroxy-3-[(2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate

Produkt 1

HCID 86587952HCID 86587952, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of [2-hydroxy-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester (313 mg, 0.93 mmol, obtained from Reference Example 14) and ethyl (2R,3R)-2-amino-3-hydroxy-3-[(2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate [400 mg, 0.93 mmol, obtained by hydrogenation of ethyl (2R,3R)-2-{[(benzyloxy)carbonyl]amino}-3-{[(benzyloxy)carbonyl]oxy}-3-[(2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate (from Reference Example 41)] in anhydrous tetrahydrofuran (7 ml) was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (53 μl) and sodium triacetoxyborohydride (395 mg, 1.86 mmol) were added, and the resulting solution was stirred for 3 hours. The reaction mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate solution and the aqueous layer was separated and extracted with ethyl acetate (2×75 ml). The combined extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative HPLC (250×21 mm Phenomenex Prodigy ODS3 column eluted with 10-90% acetonitrile in water containing 0.02% trifluoroacetic acid over 72 minutes) to provide ethyl (5S)-12-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate as white amorphous solid.

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate solution
  2. customthe aqueous layer was separated
  3. extractionextracted with ethyl acetate (2×75 ml)
  4. washThe combined extracts were washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative HPLC (250×21 mm Phenomenex Prodigy ODS3 column eluted with 10-90% acetonitrile in water containing 0.02% trifluoroacetic acid over 72 minutes)

Quellen und Nachweise

ORD-Eintrag
ord-42b1851ae529449aad983940f47d81ae
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06858591B2

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