Sodium hydride → HCID 57546114, compound

HRID 913863Notes

Reaction equation

HRID 913863 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][OH:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[CH:24]([C:26]1[C:34]2[C:30](=[CH:31][N:32]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:33]=2)[CH:29]=[C:28]([O:43][CH3:44])[CH:27]=1)[CH3:25].[H-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:21][O:22][CH:24]([C:26]3[C:34]4[C:30](=[CH:31][N:32]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:42])[CH3:41])[N:33]=4)[CH:29]=[C:28]([O:43][CH3:44])[CH:27]=3)[CH3:25])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546057HCID 57546057, compound

Product 1

HCID 57546114HCID 57546114, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (193 mg, 0.66 mmol) and 7-(1-bromoethyl)-5-methoxy-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole (240 mg, 0.623 mmol) in dimethylformamide (2.5 mL) at 0° C. was added sodium hydride (60% in mineral oil, 32.4 mg, 0.81 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 (15%→25% EtOAc/Hex) gave 29 mg (7.6%) as oil. 1H-NMR (CDCl3, 300 MHz) δ 7.88 (s, 1H), 7.25-7.30 (m, 2H), 6.95-7.00 (m, 2H), 6.6606.71 (m, 2H), 5.60 (s, 2H), 4.88 (q, J=6.0 Hz, 1H), 3.77 (s, 3H), 3.66-3.71 (m, 2H), 3.53-3.59 (m, 2H), 3.28-3.41 (m, 2H), 1.40 (m, 12H), 0.85-0.9 (m, 2H), -0.08 (s, 9H), 13C-NMR (CDCl3, 76 MHz) δ 161.2 (d, J=972 Hz), 155.5, 154.9, 143.9, 138.8, 135.3, 128.8, 122.3, 121.5, 116.1, 115.0, 114.7, 94.9, 81.4, 79.2, 73.9, 67.0, 60.3, 55.1, 41.2, 31.8, 28.4, 22.6, 20.9, 17.7, 14.1, −1.6; Mass spec.: 614.63 (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 (15%→25% EtOAc/Hex) gave 29 mg (7.6%) as oil

Sources & evidence

ORD record
ord-76d4143d040d4bb188002766c6942971
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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