Sodium hydride → tert-Butyl 4-((5-bromo-2-methoxy-3-methylbenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 391447Notes

Reaction equation

HRID 391447 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([O:10][CH3:11])=[C:6]([CH2:8]Br)[CH:7]=1.[OH:13][CH2:14][C:15]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.[H-].[Na+]>CN(C)C=O.O>[Br:1][C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([O:10][CH3:11])=[C:6]([CH:7]=1)[CH2:8][O:13][CH2:14][C:15]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 589936415-Bromo-2-methoxy-3-methylbenzyl bromide

Product 1

HCID 58993511tert-Butyl 4-((5-bromo-2-methoxy-3-methylbenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-Bromo-1-(bromomethyl)-2-methoxy-3-methylbenzene (0.88 g, 3.0 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.79 g, 2.7 mmol) were combined in dimethylformamide (9 mL) and cooled to 0° C. The reaction was treated with sodium hydride (144 mg, 5.99 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 (10% ethyl acetate/hexanes) gave 1.24 g (82%). 1H-NMR (CDCl3, 500 MHz) δ 7.34-7.35 (m, 4H), 7.21-7.24 (m, 1H), 7.19-7.20 (m, 1H), 7.10 (m, 1H), 4.34 (s, 2H), 3.72-3.76 (m, 2H), 3.53 (s, 3H), 3.43 (s, 2H), 3.01-3.07 (m, 2H), 2.21 (s, 3H), 2.17-2.19 (m, 2H), 1.85-1.91 (m, 2H), 1.43 (s, 9H). Mass spec.: 506.45 (MH)+.

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 (10% ethyl acetate/hexanes) gave 1.24 g (82%)

Sources & evidence

ORD record
ord-c50a03554759417ea7fa1df68940f400
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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