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

HRID 913801Notes

Reaction equation

HRID 913801 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11]Br)[CH:10]=1)[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:6]=[CH:5]2.[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:3]=[C:4]2[C:8](=[C:9]([CH2:11][O:21][CH2:22][C:23]3([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])[CH2:25][CH2:24]3)[CH:10]=1)[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:6]=[CH:5]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 575461635-bromo-7-(bromomethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

Product 1

HCID 57545925tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-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)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (220 mg, 0.52 mmol), tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (160 mg, 0.55 mmol), and dimethylformamide (2.5 mL). The reaction was cooled to 0° C. and treated with sodium hydride (26.4 mg, 1.1 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 233 mg (71%) as a gum. 1H-NMR (CDCl3, 500 MHz) δ 7.87 (s, 1H), 7.78 (d, J=1.5 Hz, 1H), 7.27 (d, J=1.8 Hz, 1H), 7.19 (m, 5H), 5.32 (s, 2H), 4.65 (s, 2H), 3.67 (bs, 2H), 3.41 (s, 2H), 3.36 (t, J=8.2 Hz, 2H), 3.00 (m, 2H), 2.11 (m, 2H), 1.76 (m, 2H), 1.41 (s, 9H), 0.75 (t, J=8.2 Hz, 2H), −0.10 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.0, 142.7, 137.1, 133.1, 131.4, 128.4, 127.8, 127.1, 126.4, 123.5, 122.8, 113.7, 79.4, 79.1, 78.8, 70.4, 66.0, 41.5, 40.2 (br), 32.1, 28.6, 17.8, −1.40.

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 233 mg (71%) as a gum

Sources & evidence

ORD record
ord-7daf689baf7640a1ad4b2eecd14bfc98
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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