Sodium hydride → HCID 57546147, compound

HRID 913798Notes

Reaction equation

HRID 913798 reaction equation
[OH:1][CH2:2][C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.Br[CH2:23][C:24]1[CH:32]=[C:31]([CH3:33])[C:30]2[C:26](=[CH:27][N:28]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[N:29]=2)[CH:25]=1.[H-].[Na+]>CN(C)C=O>[CH3:33][C:31]1[C:30]2[C:26](=[CH:27][N:28]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:39])([CH3:41])[CH3:40])[N:29]=2)[CH:25]=[C:24]([CH2:23][O:1][CH2:2][C:3]2([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[CH:32]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 575462295-(Bromomethyl)-7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole

Product 1

HCID 57546147HCID 57546147, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (102 mg, 0.350 mmol) and 5-(bromomethyl)-7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole (113 mg, 0.318 mmol) in dimethylformamide (0.75 mL) at 0° C. was added sodium hydride (16.8 mg, 0.70 mmol). The resulting solution was stirred at at 0° C. for 30 min. The reaction was quenched by the cautious addition of saturated ammonium chloride and diluted with diethyl ether. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12%→25% EtOAc/Hex) gave 170 mg (94%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.31-7.40 (m, 4H), 7.25 (m, 1H), 7.21 (s, 1H), 6.79 (s, 1H), 5.70 (s, 2H), 4.37 (s, 2H), 3.73 (bs, 2H), 3.63 (m, 2H), 3.40 (s, 2H), 3.04 (m, 2H), 2.57 (s, 3H), 2.16 (m, 2H), 1.91 (m, 2H), 1.43 (s, 9H), 0.94 (m, 2H), −0.03 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 155.1, 149.2, 143.3, 132.5, 128.5, 128.1, 127.4, 126.3, 125.7, 122.9, 121.9, 116.1, 81.8, 79.3, 78.9, 73.8, 67.4, 41.8, 40.1 (br), 32.0, 28.6, 18.0, 17.2, −1.3.

Workup

  1. customThe reaction was quenched by the cautious addition of saturated ammonium chloride
  2. additiondiluted with diethyl ether
  3. washThe ethereal was washed with water (2×)
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customColumn chromatography (12%→25% EtOAc/Hex) gave 170 mg (94%) as a colorless oil

Sources & evidence

ORD record
ord-2e81e6ff06834a71820365e8a44fab8e
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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