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

HRID 391427Notes

Reaction equation

HRID 391427 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([CH2:9]Br)[CH:3]=1.[OH:11][CH2:12][C:13]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.[H-].[Na+]>CN(C)C=O.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([F:8])[CH:7]=1)[CH2:9][O:11][CH2:12][C:13]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 235096191-Bromo-3-(bromomethyl)-5-fluorobenzene

Product 1

HCID 58993701tert-Butyl 4-((3-bromo-5-fluorobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-Bromo-3-(bromomethyl)-5-fluorobenzene (0.8 g, 3.0 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.72 g, 2.5 mmol) were combined in dimethylformamide (8 mL) and cooled to 0° C. The reaction was treated with sodium hydride (120 mg, 4.98 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 1.2 g (84%). 1H-NMR (CDCl3, 500 MHz) δ 7.34-7.38 (m, 4H), 7.24-7.25 (m, 1H), 7.08-7.10 (m, 1H), 7.01 (s, 1H), 6.70-6.72 (m, 1H), 4.29 (s, 2H), 3.74-3.77 (m, 2H), 3.38 (s, 2H), 3.00-3.06 (m, 2H), 2.17-2.20 (m, 2H), 1.84-1.90 (m, 2H), 1.44 (s, 9H). Mass spec.: 501.32 (MNa)+.

Workup

  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 1.2 g (84%)

Sources & evidence

ORD record
ord-892b351a603f47b4bd7bcde1b9da5e68
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

Loading…