Acetic Acid → tert-butyl(2S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3,3-dimethylbutanoate

HRID 1174129Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1174129
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH:13]=O.Cl.[C:16]([O:20][C:21](=[O:28])[C@H:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[NH2:23])([CH3:19])([CH3:18])[CH3:17].C([BH3-])#N.[Na+].C(O)(=O)C>CO.C(Cl)(Cl)Cl.C(OCC)(=O)C>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][NH:23][C@@H:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:21]([O:20][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:28]

Komponenten

8

Edukt 4

HCID 176Acetic AcidHCID 76201Phthalylglycine aldehydeHCID 5003444Sodium cyanoborohydrideHCID 56776989tert-butyl (2S)-2-amino-3,3-dimethylbutanoate hydrochloride

Produkt 1

HCID 67407870tert-butyl(2S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3,3-dimethylbutanoateAusbeute 64,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of the product of Example 3E (9.34 g, 49.4 mmol) in methanol (33 mL) was treated with L-tert-leucine tert-butyl ester hydrochloride (10 g, 44.9 mmol), sodium cyanoborohydride (5.6 g, 89.8 mmol), and acetic acid (1.5 ml, 26.2 mmol), stirred at 25° C. for 4 hours, and partitioned between chloroform and saturated NaHCO3. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel, eluting with first with 66% chloroform in hexanes and then with 33% ethyl acetate in chloroform to give the title compound (10.5 g, 59% yield).

Aufarbeitung

  1. custompartitioned between chloroform and saturated NaHCO3
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel
  7. washeluting with first with 66% chloroform in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-00a8a93ce66e464f9983543c2997f649
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07834043B2

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