Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate → Tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 656508Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 656508
Br[CH2:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[C:5]([Cl:13])[N:4]=1.[OH:14][CH2:15][C:16]1([C:29]2[CH:34]=[CH:33][CH:32]=[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.CC(C)([O-])C.[K+]>O1CCCC1.O>[Cl:13][C:5]1[N:4]=[C:3]([CH2:2][O:14][CH2:15][C:16]2([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=1

Komponenten

6

Edukt 3

HCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 534037392-(Bromomethyl)-6-chloro-4-(trifluoromethyl)pyridine

Produkt 1

HCID 57557581Tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2-(bromomethyl)-6-chloro-4-(trifluoromethyl)pyridine (1.1 g, 4.1 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (1.0 g, 3.4 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. The reaction was treated with potassium tert-butoxide (763 mg, 6.8 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 837 mg (52%). 1H-NMR (CDCl3, 400 MHz) δ 7.31-7.38 (m, 6H), 7.18 (s, 1H), 4.48 (s, 2H), 3.74-3.79 (m, 2H), 3.50 (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.: 485.11 (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 837 mg (52%)

Quellen und Nachweise

ORD-Eintrag
ord-9ff67bebf1504c34a46cb9eee942a14e
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071778B2

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