Lithium Hydroxide → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(tetrahydropyran-2-carbonyl)amino]pentanoic Acid

HRID 508400

Reaktionsgleichung

Reaktionsgleichung von HRID 508400
C([O:3][C:4](=[O:24])[C@H:5]([OH:23])[CH2:6][C@H:7]([NH2:22])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:11][CH:10]=1)C.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Li+].[OH-]>CN(C=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([C:12]2[CH:13]=[CH:14][C:9]([CH2:8][C@@H:7]([NH:22][C:31]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30][O:25]3)=[O:32])[CH2:6][C@@H:5]([OH:23])[C:4]([OH:3])=[O:24])=[CH:10][CH:11]=2)[CH:20]=[CH:19][CH:18]=1

Komponenten

7

Edukt 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10964532Oxane-2-carboxylic acidHCID 86682253(2R,4R)-4-amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester

Produkt 1

HCID 90387417(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(tetrahydropyran-2-carbonyl)amino]pentanoic AcidAusbeute 52,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(2R,4R)-4-Amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (50 mg, 144 μmol) was added to a solution of tetrahydro-pyran-2-carboxylic acid (1.2 eq., 165 μmol) and HATU (71.1 mg, 187 μmol) in DMF (250 μL), followed by the addition of DIPEA (75 μL, 431 μmol). The resulting mixture was stirred at room temperature for 1 hour. 10 M aqueous LiOH (115 μL, 1.2 mmol) was added and the mixture was stirred for an additional 1 hour. The mixture was washed with DCM (1 mL) and the aqueous layer was acidified with concentrated HCl (250 μL) and extracted with DCM (2×1 mL). The DCM extracts were combined and concentrated in vacuo, and the resulting crude liquid was purified by reverse phase preparative HPLC to yield the title compound (32.6 mg). MS m/z [M+H]+ calc'd for C23H26ClNO5, 432.15. found 432.2.

Aufarbeitung

  1. stirringthe mixture was stirred for an additional 1 hour
  2. washThe mixture was washed with DCM (1 mL)
  3. extractionextracted with DCM (2×1 mL)
  4. concentrationconcentrated in vacuo
  5. customthe resulting crude liquid was purified by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-66aa00106297452ca21f25fe31250cac
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096496B2

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