Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → Tert-butyl 4-(((5-bromopryidin-3-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 656511

Reaktionsgleichung

Reaktionsgleichung von HRID 656511
[Br:1][CH2:2][C:3]1C=C(C(F)(F)F)C=C(Cl)[N:4]=1.[OH:14][CH2:15][C:16]1([C:29]2[CH:34]=[CH:33][C:32](F)=[CH:31][CH:30]=2)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[CH3:36][C:37]([CH3:40])([O-])[CH3:38].[K+]>O1CCCC1.O>[Br:1][C:2]1[CH:36]=[C:37]([CH2:40][O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:38]=[N:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 53403739HCID 53403739, Verbindung

Produkt 1

HCID 57557588Tert-butyl 4-(((5-bromopryidin-3-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyllpiperidine-1-carboxylate. 2-(bromomethyl)-6-chloro-4-(trifluoromethyl)pyridine (301 mg, 1.1 mmol) and tert-butyl 4-(hydroxymethyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (309 mg, 1.0 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. The reaction was treated with potassium tert-butoxide (244 mg, 2.0 mmol) portion wise. The reaction was stirred at 0° C. for 1 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over magnesium sulfate, and concentrated. Column chromatography on silica gel (10% ethyl acetate/hexanes) gave 215 mg (43%). 1H-NMR (CDCl3, 400 MHz) δ 7.38 (s, 1H), 7.29-7.36 (m, 2H), 7.14 (s, 1H), 7.01-7.10 (m, 2H), 4.48 (s, 2H), 3.74-3.79 (m, 2H), 3.47 (s, 2H), 2.99-3.06 (m, 2H), 2.21-2.25 (m, 2H), 1.83-1.86 (m, 2H), 1.42 (s, 9H). Mass spec.: 403.08 (MH)+.

Aufarbeitung

  1. extractionextracted with ethyl acetate (2×)
  2. washwashed with brine (2×)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customColumn chromatography on silica gel (10% ethyl acetate/hexanes) gave 215 mg (43%)

Quellen und Nachweise

ORD-Eintrag
ord-801d8e44da0b4633a8c6dc2252e63cb5
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071778B2

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