Methanesulfonic Acid → 3-(1-Adamantyl)-4-bromo-5-methoxyphenol

HRID 508668Notes

Reaction equation

HRID 508668 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[O:9][CH3:10].[C:11]12(O)[CH2:20][CH:15]3[CH2:16][CH:17]([CH2:19][CH:13]([CH2:14]3)[CH2:12]1)[CH2:18]2.CS(O)(=O)=O>C(Cl)Cl>[C:11]12([C:7]3[CH:6]=[C:5]([OH:8])[CH:4]=[C:3]([O:9][CH3:10])[C:2]=3[Br:1])[CH2:20][CH:15]3[CH2:16][CH:17]([CH2:19][CH:13]([CH2:14]3)[CH2:12]1)[CH2:18]2.[C:11]12([C:6]3[CH:7]=[C:2]([Br:1])[C:3]([O:9][CH3:10])=[CH:4][C:5]=3[OH:8])[CH2:20][CH:15]3[CH2:16][CH:17]([CH2:19][CH:13]([CH2:14]3)[CH2:12]1)[CH2:18]2

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 641521-AdamantanolHCID 3479554-Bromo-3-methoxyphenol

Product 2

HCID 672090503-(1-Adamantyl)-4-bromo-5-methoxyphenolYield 55%HCID 873106562-(1-Adamantyl)-4-bromo-5-methoxyphenolYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
54 °C

Procedure

A mixture of 4-bromo-3-methoxyphenol (6.33 g, 31.18 mmol), 1-adamantanol (4.75 g, 31.18 mmol) and MeSO3H (1.3 mL) in CH2Cl2 (22 mL) was stirred with heating at 54° C. (oil-bath) for 29 h. The resulting solution was quenched with H2O (30 mL) and extracted with EtOAc (140 mL). The extract was washed with H2O, 5% NaHCO3, and brine and dried. The residue obtained on concentration was purified on silica gel (0% to 15% EtOAc/hexane) to give 5.77 g (55%) of 3-(1-adamantyl)-4-bromo-5-methoxyphenol as a white solid, mp 151-153° C. and 2.71 g (26%) of 2-(1-adamantyl)-4-bromo-5-methoxyphenol as a white solid, mp 182-185° C. 3-(1-Adamantyl)-4-bromo-5-methoxyphenol: IR 3515, 2902, 2848, 1312, 1216 cm−1; 1H NMR δ (CDCl3) 1.75 (bs, 6H, AdCH2), 2.04 (bs, 9H, AdCH and AdCH2), 3.79 (s, 311, OCH3), 5.29 (s, 1H, OH), 6.57 (s, 1H, 6-ArH), 7.19 ppm (s, 1H, 2-ArH). 2-(1-Adamantyl)-4-bromo-5-methoxyphenol: IR 3513, 2902, 2848, 1389, 1207 cm−1; 1H NMR δ (CDCl3) 1.77 (bs, 6H, AdCH2), 2.06 (bs, 9H, AdCH and AdCH2), 3.83 (s, 3H, OCH3), 4.83 (s, 1H, OH), 6.29 (s, 1H, 6-ArH), 7.31 ppm (s, 1H, 3-ArH).

Workup

  1. customThe resulting solution was quenched with H2O (30 mL)
  2. extractionextracted with EtOAc (140 mL)
  3. washThe extract was washed with H2O, 5% NaHCO3, and brine
  4. customdried
  5. customThe residue obtained on concentration
  6. customwas purified on silica gel (0% to 15% EtOAc/hexane)

Sources & evidence

ORD record
ord-25aa1d2b1ca14d84ad5e9fb90a0a1899
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

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