alpha-Chlorohydrin, (+)- → (S)-3-{4-[3-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol

HRID 245118Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245118
[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[N:16]=[C:15]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([OH:24])=[C:19]([CH2:25][CH3:26])[CH:18]=4)[O:14][N:13]=3)[CH:9]=[C:8]([O:27][CH3:28])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:30][C@@H:31]([OH:34])[CH2:32][OH:33]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[N:16]=[C:15]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([O:24][CH2:30][C@@H:31]([OH:34])[CH2:32][OH:33])=[C:19]([CH2:25][CH3:26])[CH:18]=4)[O:14][N:13]=3)[CH:9]=[C:8]([O:27][CH3:28])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

6

Edukt 2

HCID 148904alpha-Chlorohydrin, (+)-HCID 1363910174-[3-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenol

Produkt 1

HCID 49872263(S)-3-{4-[3-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diolAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3776IsopropanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenol (150 mg, 395 μmol) and (S)-3-chloro-propane-1,2-diol (366 mg, 3.31 mmol) in isopropanol (4 mL) and 3 N aq. NaOH (1 mL) is stirred at 70° C. for 48 h. The mixture is diluted with EA (50 mL), washed with 1 M aq. NaOH solution (20 mL) followed by brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (95 mg) as a pale brown oil; LC-MS**: tR=0.88 min, [M+H]+=454.08; 1H NMR (CDCl3): δ1.34 (t, J=7.0 Hz, 3H), 1.67-1.79 (m, 2H), 1.82-1.96 (m, 4H), 2.04-2.15 (m, 2H), 2.43 (s, 3H), 2.79 (q, J=7.0 Hz, 2H), 3.18-3.29 (m, 1H), 3.81-3.99 (m, 4H), 4.01 (s, 3H), 4.15-4.22 (m, 1H), 7.30 (s, 1H), 7.49 (s, 1H), 7.93 (s, 1H), 7.94 (s, 1H).

Aufarbeitung

  1. washwashed with 1 M aq. NaOH solution (20 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified by prep

Quellen und Nachweise

ORD-Eintrag
ord-a1a666bc0b93495eb92f2bd4d89b1be2
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658675B2

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