Sodium hydride → HCID 58993666, compound

HRID 391441Notes

Reaction equation

HRID 391441 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:5]=[C:6]([CH2:8]Br)[CH:7]=1.[OH:17][CH2:18][C:19]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1.[H-].[Na+]>CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[C:6]([CH2:8][O:17][CH2:18][C:19]2([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH2:21][CH2:20]2)[CH:5]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 58993580HCID 58993580, compound

Product 1

HCID 58993666HCID 58993666, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Bromo-5-(bromomethyl)-4′-fluorobiphenyl (398 mg, 1.16 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (280 mg, 0.96 mmol) were combined in dimethylformamide (5 mL) and cooled to 0° C. The reaction was treated with sodium hydride (46 mg, 1.92 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 470 mg (73%). 1H-NMR (CDCl3, 500 MHz) δ 7.51 (s, 1H), 7.28-7.42 (m, 6H), 7.19-7.23 (m, 2H), 7.06-7.14 (m, 3H), 4.34 (s, 2H), 3.69-3.74 (m, 2H), 3.40 (s, 2H), 2.98-3.06 (m, 2H), 2.14-2.19 (m, 2H), 1.81-1.90 (m, 2H), 1.41 (s, 9H). Mass spec.: 556.37 (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 (20% ethyl acetate/hexanes) gave 470 mg (73%)

Sources & evidence

ORD record
ord-2868932f3a4d4af186e54828b835c504
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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