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

HRID 391414Notes

Reaction equation

HRID 391414 reaction equation
Br[CH2:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[O:12][CH3:13].[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>[CH3:13][O:12][C:4]1[CH:5]=[CH:6][C:7]([N+:9]([O-:11])=[O:10])=[CH:8][C:3]=1[CH2:2][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

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 775162-(Bromomethyl)-1-methoxy-4-nitrobenzeneHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 58993459tert-Butyl 4-((2-methoxy-5-nitrobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-(Bromomethyl)-1-methoxy-4-nitrobenzene (100.0 mg, 0.34 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (93.0 mg, 0.38 mmol) were combined in dimethylformamide (4 mL) and cooled to 0° C. The reaction was treated with sodium hydride (9.0 mg, 0.38 mmol), stirred at 0° C. for 1 hr 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 (15% ethyl acetate/hexanes) gave 110 mg (71%). 1H-NMR (CDCl3, 500 MHz) δ 8.11 (dd, J=6.1, 3.1 Hz, 1H), 8.08 (d, J=2.8 Hz, 1H), 7.34 (m, 4H), 7.21-7.24 (m, 1H), 6.80 (d, J=8.9 Hz, 1H), 4.37 (s, 2H), 3.85 (s, 3H), 3.74-3.75 (m, 2H), 3.48 (s, 2H), 3.02-3.07 (m, 2H), 2.21-2.24 (m, 2H), 1.87-1.93 (m, 2H), 1.43 (s, 9H). Mass spec.: 479.16 (MNa)+.

Workup

  1. extractionextracted with ethyl acetate (2×)
  2. washwashed with brine (2×)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customColumn chromatography on silica gel (15% ethyl acetate/hexanes) gave 110 mg (71%)

Sources & evidence

ORD record
ord-c81ed16ef050480ab5afc1990e52d538
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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