Sodium hydride → HCID 58993686, compound

HRID 391431Notes

Reaction equation

HRID 391431 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[CH:6]=[C:7]([Cl:9])[CH:8]=1.[OH:18][CH2:19][C:20]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1.[H-].[Na+]>CN(C)C=O.O>[Cl:9][C:7]1[CH:8]=[C:3]([CH2:2][O:18][CH2:19][C:20]2([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[CH2:22][CH2:21]2)[CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[CH:6]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 58993479HCID 58993479, compound

Product 1

HCID 58993686HCID 58993686, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3′-(Bromomethyl)-5′-chlorobiphenyl-4-carbonitrile (38.3 mg, 0.12 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (30.3 mg, 0.1 mmol) were combined in dimethylformamide (2 mL) and cooled to 0° C. The reaction was treated with sodium hydride (5 mg, 0.2 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 (25% ethyl acetate/hexanes) gave 35 mg (56%). 1H-NMR (CDCl3, 300 MHz) δ 7.71 (s, 1H), 7.68 (s, 1H), 7.55 (s, 1H), 7.52 (s, 1H), 7.39 (s, 1H), 7.28-7.35 (m, 4H), 7.19-7.21 (m, 1H), 7.10-7.13 (m, 2H), 4.36 (s, 2H), 3.69-3.76 (m, 2H), 3.41 (s, 2H), 2.97-3.06 (m, 2H), 2.15-2.19 (m, 2H), 1.80-1.90 (m, 2H), 1.40 (s, 9H). Mass spec.: 517.21 (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 (25% ethyl acetate/hexanes) gave 35 mg (56%)

Sources & evidence

ORD record
ord-9fc544b77009428fa50466eca1152646
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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