Sodium hydride → HCID 57546071, compound

HRID 913823Notes

Reaction equation

HRID 913823 reaction equation
[Br:1][C:2]1[N:3]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[N:4]=[C:5]2[C:10]=1[CH:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:7]=[C:6]2[CH2:15]Br.[OH:25][CH2:26][C:27]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.[H-].[Na+]>CN(C)C=O.O>[Br:1][C:2]1[N:3]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:22])([CH3:23])[CH3:24])[N:4]=[C:5]2[C:10]=1[CH:9]=[C:8]([C:11]([F:13])([F:12])[F:14])[CH:7]=[C:6]2[CH2:15][O:25][CH2:26][C:27]1([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 57546129HCID 57546129, compound

Product 1

HCID 57546071HCID 57546071, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Bromo-7-(bromomethyl)-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole (140 mg, 0.29 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (75 mg, 0.26 mmol) were combined in dimethylformamide (2 mL) and cooled to 0° C. The reaction was treated with sodium hydride (14 mg, 0.57 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%→20% ethyl acetate/hexanes) gave 101 mg (50%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 7.86 (s, 1H), 7.44 (s, 1H), 7.14-7.18 (m, 5H), 5.26 (s, 2H), 4.68 (s, 2H), 3.69 (m, 2H), 3.44 (s, 2H), 3.38-3.41 (m, 2H), 2.98-3.02 (m, 2H), 2.11-2.14 (m, 2H), 1.72-1.77 (m, 2H), 1.41 (s, 9H), 0.74-0.77 (m, 2H), 0.10 (s, 9H). Mass spec.: 700.11 (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%→20% ethyl acetate/hexanes) gave 101 mg (50%) as an oil

Sources & evidence

ORD record
ord-6e8f1fa745c34cd29fccd1f1e513119d
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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