Sodium hydride → HCID 57545979, compound

HRID 913817Notes

Reaction equation

HRID 913817 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[CH:23]([C:25]1[C:33]2[C:29](=[CH:30][N:31]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[N:32]=2)[CH:28]=[C:27]([C:42]([F:45])([F:44])[F:43])[CH:26]=1)[CH3:24].[H-].[Na+]>CN(C)C=O>[C:16]1([C:3]2([CH2:2][O:1][CH:23]([C:25]3[C:33]4[C:29](=[CH:30][N:31]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:39])([CH3:41])[CH3:40])[N:32]=4)[CH:28]=[C:27]([C:42]([F:45])([F:44])[F:43])[CH:26]=3)[CH3:24])[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:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 57546133HCID 57546133, compound

Product 1

HCID 57545979HCID 57545979, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (193 mg, 0.66 mmol) and 7-(1-bromoethyl)-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole (280 mg, 0.66 mmol) in dimethylformamide (2.5 mL) at 0° C. was added sodium hydride (60% in mineral oil, 34.4 mg, 0.86 mmol). The resulting solution was stirred 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%→20% EtOAc/Hex) gave 62 mg (15%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 8.24 (s, 1H), 7.94 (s, 1H), 7.32-7.45 (m, 4H), 7.23-7.29 (m, 2H), 5.75 (m, 2H), 5.04 (q, J=6.4 Hz, 1H), 3.81 (m, 2H), 3.67 (m, 2H), 3.44 (qAB, JAB=9.2 Hz, 2H), 3.10 (m, 2H), 2.23 (m, 2H), 2.03 (m, 2H), 1.52 (d, J=6.4 Hz, 3H), 1.48 (s, 9H), 0.97 (m, 2H), 0.00 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.2, 147.4, 142.9, 135.5, 128.5, 127.3, 126.4, 124.8 (q, J=272 Hz), 124.7 (q, J=32 Hz), 124.6, 121.1, 117.9 (q, J=4.8 Hz), 117.3 (q, J=2.9 Hz), 82.0, 79.3, 78.2, 74.1, 67.8, 41.8, 40.3 (br), 31.8, 28.6, 22.8, 17.9, −1.4. Mass spec.: 634.17 (MH)+.

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%→20% EtOAc/Hex) gave 62 mg (15%) as an oil

Sources & evidence

ORD record
ord-a61e69716eaf4f00934547d381fea958
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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