Sodium hydride → tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 391379

Reaktionsgleichung

Reaktionsgleichung von HRID 391379
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([CH2:12]Br)[CH:3]=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.[H-].[Na+]>CN(C)C=O.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1)[CH2:12][O:14][CH2:15][C:16]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][CH2:17]1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 223242723-Bromo-5-(trifluoromethyl)benzyl bromide

Produkt 1

HCID 58993603tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

1-Bromo-3-(bromomethyl)-5-(trifluoromethyl)benzene (1.0 g, 3.14 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.70 g, 2.4 mmol) were combined in dimethylformamide (8 mL) and cooled to 0° C. The reaction was treated with sodium hydride (115 mg, 4.8 mmol), stirred at 0° C. for 1 h, and at room temperature for 30 min. 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 sodium sulfate, and concentrated. Column chromatography on silica gel (20% ethyl acetate/hexanes) gave 1.6 g (96%). 1H-NMR (CDCl3, 500 MHz) δ 7.61 (s, 1H), 7.39 (s, 1H), 7.34-7.37 (m, 4H), 7.25-7.28 (m, 2H), 4.35 (s, 2H), 3.75-3.77 (m, 2H), 3.41 (s, 2H), 3.01-3.06 (m, 2H), 2.19-2.22 (m, 2H), 1.83-1.89 (m, 2H), 1.44 (s, 9H). Mass spec.: 530.21 (MH)+.

Aufarbeitung

  1. waitat room temperature for 30 min
  2. extractionextracted with ethyl acetate (2×)
  3. washwashed with brine (2×)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customColumn chromatography on silica gel (20% ethyl acetate/hexanes) gave 1.6 g (96%)

Quellen und Nachweise

ORD-Eintrag
ord-6be90bf306a4426086129711f34beb4c
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08383821B2

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