Ethyl Acetate → (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

HRID 1396930Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396930
[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8](F)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:23]1([CH2:29][O:30][C:31]([N:33]2[CH2:37][CH2:36][C@@H:35]([C:38]([OH:40])=[O:39])[NH:34]2)=[O:32])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CCN(C(C)C)C(C)C.C(OCC)(=O)C>ClCCl.C(O)(=O)C.CC#N>[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8]([N:34]2[C@H:35]([C:38]([OH:40])=[O:39])[CH2:36][CH2:37][N:33]2[C:31]([O:30][CH2:29][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:32])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

8

Edukt 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 68287653(S)-1-((Benzyloxy)carbonyl)pyrazolidine-3-carboxylic acidHCID 86706340(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride

Produkt 1

HCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acidAusbeute 61,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride (4 g, 13.01 mmol) was added into the solution of (3S)-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidine carboxylic acid (3.91 g, 15.62 mmol) in dichloromethane (DCM) (46.1 ml), followed by adding Hunig's base (6.80 ml, 39.0 mmol). The reaction mixture was stirred at ambient temperature for 5 hrs. The reaction was diluted with DCM, and acetic acid (10 ml) was added. The resulting solution was washed with aqueous NH4Cl (200 ml). The aqueous solution was extracted with DCM (2×50 ml). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give a residue. Ethyl acetate (a few ml) was added. The desired product was filtered and washed with ethyl acetate. 3.21 g of desired product was collected as a white solid. The filtrate was purified by silica gel chromatography (0-100% ethyl acetate in hexane) to give a solid. The solid was added to 10 ml of MeCN. Another batch of the desired product (1.081 g) as a white solid was collected via filtration. These two batches of desired products were combined to yield (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (4.291 g, 7.98 mmol, 61% yield). MS (ES+) m/z 538.0 (MH+).

Aufarbeitung

  1. additionwas added
  2. washThe resulting solution was washed with aqueous NH4Cl (200 ml)
  3. extractionThe aqueous solution was extracted with DCM (2×50 ml)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue
  8. filtrationThe desired product was filtered
  9. washwashed with ethyl acetate
  10. custom3.21 g of desired product was collected as a white solid
  11. customThe filtrate was purified by silica gel chromatography (0-100% ethyl acetate in hexane)
  12. customto give a solid
  13. filtrationAnother batch of the desired product (1.081 g) as a white solid was collected via filtration

Quellen und Nachweise

ORD-Eintrag
ord-b71d727c9dd948f3a05e4d469119a711
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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