Benzyl Bromide → 5-(1-Adamantyl)-4-benzyloxy-2-methoxyphenyl bromide

HRID 508669Notes

Reaction equation

HRID 508669 reaction equation
[C:1]12([C:11]3[CH:16]=[C:15]([Br:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=3[OH:20])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:1]12([C:11]3[C:12]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:13][C:14]([O:18][CH3:19])=[C:15]([Br:17])[CH:16]=3)[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 873106562-(1-Adamantyl)-4-bromo-5-methoxyphenol

Product 1

HCID 672090725-(1-Adamantyl)-4-benzyloxy-2-methoxyphenyl bromideYield 76.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of 2-(1-adamantyl)-4-bromo-5-methoxyphenol (2.59 g, 7.68 mmol) in acetone (26 mL) was added benzyl bromide (1.31 g, 7.68 mmol) followed by K2CO3 (1.33 g, 9.60 mmol). The mixture was stirred and heated at reflux for 17.25 h under argon. Acetone was removed at reduced pressure before 1 N HCl (40 mL) was added. The mixture was extracted with EtOAc (100 mL), and the organic layer was washed with H2O and brine and dried. After removal of solvent at reduced pressure, the residue was purified on silica gel (0% to 4% EtOAc/hexane) to give 2.50 g (76%) of 5-(1-adamantyl)-4-benzyloxy-2-methoxyphenyl bromide as a white solid, mp 124-126° C. IR 2902, 2847, 1498, 1161 cm−1; 1H NMR (CDCl3) δ 1.71 (bs, 6H, AdCH2), 2.02 (bs, 311, AdCH), 2.08 (bs, 6H, AdCH2), 3.82 (s, 3H, OCH3), 5.12 (s, 2H, C6H5CH2), 6.53 (s, 1H, 3-ArH), 7.34 (s, 1H, 6-ArH), 7.31-7.50 ppm (m, 5H, C6H5).

Workup

  1. temperatureheated
  2. temperatureat reflux for 17.25 h under argon
  3. customAcetone was removed at reduced pressure before 1 N HCl (40 mL)
  4. additionwas added
  5. extractionThe mixture was extracted with EtOAc (100 mL)
  6. washthe organic layer was washed with H2O and brine
  7. customdried
  8. customAfter removal of solvent at reduced pressure
  9. customthe residue was purified on silica gel (0% to 4% EtOAc/hexane)

Sources & evidence

ORD record
ord-e35bf2f15411434d96e1019b5229b4a0
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

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