Sodium hydride → HCID 59371591, compound

HRID 2095449Notes

Reaction equation

HRID 2095449 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][CH2:25][C:24]2[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:29])[F:30])=[CH:28][CH:27]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 59371591HCID 59371591, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-4-(2-hydroxyethyl)piperidine (302 mg, 1.32 mmol) in anhydrous THF (10 mL) was cooled to 0° C., and NaH (60% dispersion in oil, 63 mg, 1.58 mmol, 1.2 equiv.) was added all at once. Alkoxide formation was effected by stirring at room temperature for 2 h under N2, then 4-(trifluoromethyl)benzyl bromide (378 mg, 1.58 mmol, 1.2 equiv.) was added. The mixture was stirred at room temperature overnight. Saturated aqueous NH4Cl solution was added, and the product was extracted into EtOAc. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by CC (SiO2, EtOAc/hexane 1:4) to afford the ether (496 mg, 97%) after evaporation. 1H NMR (CDCl3, 400 MHz) δ 7.59 (d, 2H, J=8.4 Hz), 7.43 (d, 2H, J=8.0 Hz), 4.54 (s, 2H), 4.06 (d, 2H, J=13.2 Hz), 5.31 (t, 2H, J=6.4 Hz), 2.68 (t, 2H, J=12.8 Hz), 1.58 (m, 5H), 0.89 (m, 2H).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. extractionthe product was extracted into EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by CC (SiO2, EtOAc/hexane 1:4)
  6. customto afford the ether (496 mg, 97%)
  7. customafter evaporation

Sources & evidence

ORD record
ord-ea612b676532455e89f508be38d0ce61
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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