Sodium hydride → tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 913800Notes

Reaction equation

HRID 913800 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([CH2:11]Br)[C:8]2[C:4](=[CH:5][N:6]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:7]=2)[CH:3]=1.[OH:21][CH2:22][C:23]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1.[H-].[Na+]>CN(C)C=O>[Br:1][C:2]1[CH:10]=[C:9]([CH2:11][O:21][CH2:22][C:23]2([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])[CH2:25][CH2:24]2)[C:8]2[C:4](=[CH:5][N:6]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:7]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 575462265-bromo-7-(bromomethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole

Product 1

HCID 57546228tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with 5-bromo-7-(bromomethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole (0.61 g, 1.45 mmol), tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.444 g, 1.52 mmol), and dimethylformamide (5 mL). The reaction was cooled to 0° C. and treated with sodium hydride (0.073 g, 3.05 mmol) in several portions. After stirring for 15 min, the ice bath was removed and stirring continued for 15 min. The reaction was cooled to 0° C. and quenched by the cautious addition of saturated ammonium chloride. The reaction was poured into diethyl ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12%→25% EtOAc/Hex) gave 720 mg (79%) as a gum. 1H-NMR (CDCl3, 500 MHz) δ 8.00 (s, 1H), 7.70 (d, J=1.5 Hz, 1H), 7.38 (m, 4H), 7.24 (m, 1H), 7.13 (d, J=1.5 Hz, 1H), 5.65 (s, 2H), 4.81 (s, 2H), 3.76 (bs, 2H), 3.58 (t, J=8.2 Hz, 2H), 3.53 (s, 2H), 3.06 (m, 2H), 2.22 (m, 2H), 1.95 (m, 2H), 1.44 (s, 9H), 0.91 (t, J=8.2 Hz, 2H), 0.00 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 145.5, 142.9, 130.5, 128.6, 127.4, 126.6, 126.5, 123.3, 122.2, 121.3, 116.0, 81.9, 80.0, 79.4, 68.5, 67.6, 41.9, 40.3 (br), 32.0, 28.6, 17.9, −1.3. Mass spec.: 630.14 (MH)+.

Workup

  1. customthe ice bath was removed
  2. stirringstirring
  3. waitcontinued for 15 min
  4. temperatureThe reaction was cooled to 0° C.
  5. customquenched by the cautious addition of saturated ammonium chloride
  6. additionThe reaction was poured into diethyl ether
  7. washwashed with water (3×)
  8. dry with materialbrine, dried over magnesium sulfate
  9. concentrationconcentrated
  10. customColumn chromatography (12%→25% EtOAc/Hex) gave 720 mg (79%) as a gum

Sources & evidence

ORD record
ord-930acbbee137434ebc78c9209e9b9e32
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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