Citric Acid → (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride

HRID 1396896Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396896
[F:1]C1N=C(F)N=C(F)N=1.N1C=CC=CC=1.[CH:16]1([CH2:21][C@H:22]([CH2:26][N:27]([CH:36]=[O:37])[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:23](O)=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[CH:16]1([CH2:21][C@H:22]([CH2:26][N:27]([CH:36]=[O:37])[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:23]([F:1])=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17]1

Komponenten

6

Edukt 4

HCID 311Citric AcidHCID 1049PyridineHCID 12664Cyanuric fluorideHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acid

Produkt 1

HCID 86706340(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluorideAusbeute 64,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2,4,6-Trifluoro-1,3,5-triazine (10.7 g, 79 mmol) was added into a solution of pyridine (6.4 ml, 79 mmol) and (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (WO 2009061879) (22 g, 72.0 mmol) in dichloromethane (348 ml) at room temperature. The resulting solution was stirred overnight. Dichloromethane (300 mL) was added to the reaction solution, followed by 1000 mL of 5% citric acid, and the mixture was filtrated. The solids were washed with DCM (300 ml). The organic layer of the filtrate was separated and washed with sat. NaHCO3 (2×300 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil, which was purified by silica gel chromatography (CombiFlash, Column: 220 g; 0-20% ethyl acetate in hexane; 50 min) to provide (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride (14.32 g, 64.7% yield) as a colorless oil.

Aufarbeitung

  1. filtrationthe mixture was filtrated
  2. washThe solids were washed with DCM (300 ml)
  3. customThe organic layer of the filtrate was separated
  4. washwashed with sat. NaHCO3 (2×300 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a yellow oil, which
  9. customwas purified by silica gel chromatography (CombiFlash, Column: 220 g; 0-20% ethyl acetate in hexane; 50 min)

Quellen und Nachweise

ORD-Eintrag
ord-8211daf498fc45a5839c878c1b5f95fc
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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