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Lithium Hydroxide → 1-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylic acid

HRID 1727032
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1727032
[Cl:1][C:2]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:3]=1[CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]=2[N:7]=[C:6]1[N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([O:26]CC)=[O:25])[CH2:19]1.[Li+].[OH-]>C1COCC1.O>[Cl:1][C:2]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:3]=1[CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]=2[N:7]=[C:6]1[N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([OH:26])=[O:25])[CH2:19]1
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Komponenten

5

Edukt 2

HCID 3939Lithium HydroxideHCID 57565596Ethyl 1-[7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylate

Produkt 1

HCID 100038741-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylic acidAusbeute 103,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel
HCID 8028
Tetrahydrofuran
Lösungsmittel
2×

Versuchsvorschrift

A solution of ethyl 1-[7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylate (5.0 g, 10.5 mmol) in 75 mL THF and 25 mL H2O at room temperature was treated with solid LiOH (1.8 g, 43.9 mmol). After stirring overnight the THF was removed under reduced pressure, and the residue was diluted with H2O. The aqueous layer was acidified to pH 4, and the aqueous layer was extracted with CH2Cl2. The combined extracts were concentrated under reduced pressure to give 4.9 g (>99% yield) of the title compound: 1H NMR (CDCl3, 400 MHz) δ7.18 (dt, 2H, J=8.1, 5.7), 7.14 (t, 1H, J=7.6), 6.98-6.90 (m, 1H), 5.57 (AB quartet, 2H, J=15.7, 5.7), 3.51 (s, 3H), 3.42 (dd, 1H, J=12.6, 4.0), 3.30 (s, 3H), 3.20-3.05 (m, 2 H), 2.94-2.83 (m, 1H), 2.59-2.47 (m, 1H), 2.03-1.93 (m, 1H), 1.75-1.40 (m, 3H); LRMS (ESI) m/z 450 (M+H+); TLC (hexanes:EtOAc/1:1) Rf=0.10.

Aufarbeitung

  1. customwas removed under reduced pressure
  2. additionthe residue was diluted with H2O
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. concentrationThe combined extracts were concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-c4ee5e387fc04a8f9ff27d4f2b2b53be
Quelldatensatz
uspto-grants-2009_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07495004B2

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