Benzyl Bromide → Tert-butyl 4-(adamantan-2-yl(benzyloxy)methyl)-3-chlorobenzoate

HRID 1849750Notes

Reaction equation

HRID 1849750 reaction equation
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[CH:11]([OH:26])[C:12]1[CH:24]=[CH:23][C:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:14][C:13]=1[Cl:25])[CH2:8]2.[H-].[Na+].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[CH:11]([O:26][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:12]1[CH:24]=[CH:23][C:15]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])=[CH:14][C:13]=1[Cl:25])[CH2:8]2

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86703631Tert-butyl 4-(adamantan-2-yl(hydroxy)methyl)-3-chlorobenzoate

Product 1

HCID 86703632Tert-butyl 4-(adamantan-2-yl(benzyloxy)methyl)-3-chlorobenzoateYield 93.6%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-(adamantan-2-yl(hydroxy)methyl)-3-chlorobenzoate (0.32 mg, 1.00 mmol) in anhydrous dimethylformamide (5 mL) was added sodium hydride (60% dispersion in mineral oil, 0.048 g, 1.2 mmol) at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 hour. Benzyl bromide (0.24 mL, 2.00 mmol) and tetrabutylammonium iodide (0.037 g, 0.10 mmol) was added and the reaction mixture was stirred for 16 hours at ambient temperature. After quenched with saturated ammonium chloride solution (10 mL), the mixture was diluted with ethyl acetate (150 mL). The organic phase was washed with water (3×10 mL), brine (10 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo gave a residue which was purified by silica gel column chromatography using 0-20% ethyl acetate in hexanes as eluent to afford the title compound as a colorless oil (0.437 g, quant.): 1H NMR (300 MHz, CDCl3) δ 7.97-7.95 (m, 1H), 7.90 (d, J=8.18 Hz, 1H), 7.60 (d, J=7.39 Hz, 1H), 7.46-7.18 (m, 5H), 5.18-5.11 (m, 1H), 4.30 (d, J=11.54 Hz, 1H), 4.18 (d, J=11.60 Hz, 1H), 2.41 (s, 1H), 2.12-1.30 (m, 22H), 1.13 (s, 1H).

Workup

  1. stirringthe reaction mixture was stirred for 16 hours at ambient temperature
  2. customAfter quenched with saturated ammonium chloride solution (10 mL)
  3. additionthe mixture was diluted with ethyl acetate (150 mL)
  4. washThe organic phase was washed with water (3×10 mL), brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customConcentration of the filtrate in vacuo gave a residue which
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-845258253e874c0f8acd4b16190228cb
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

Loading…