Trifluoromethanesulfonic acid → 1-((4-Bromo-2-chloro-5-fluorobenzyl)oxy)adamantane

HRID 1427830Notes

Reaction equation

HRID 1427830 reaction equation
Cl[C:2](Cl)(Cl)[C:3](=N)[O:4][CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([Br:13])=[CH:8][C:7]=1[Cl:14].[C:18]12(O)[CH2:27]C3C[CH:24]([CH2:26][CH:20]([CH2:21]3)[CH2:19]1)[CH2:25]2.FC(F)(F)S(O)(=O)=O>C(Cl)Cl.C1CCCCC1>[Br:13][C:9]1[C:10]([F:12])=[CH:11][C:6]([CH2:5][O:4][C:3]23[CH2:27][CH:18]4[CH2:19][CH:20]([CH2:26][CH:24]([CH2:25]4)[CH2:2]2)[CH2:21]3)=[C:7]([Cl:14])[CH:8]=1

Participants

6

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 641521-AdamantanolHCID 867028534-Bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate

Product 1

HCID 867028541-((4-Bromo-2-chloro-5-fluorobenzyl)oxy)adamantaneYield 44%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8078CyclohexaneSolvent

Procedure

To a solution of 4-bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate (3.95 g, 16.49 mmol) and 1-adamantanol (0.65 g, 4.26 mmol) in methylene chloride (15 mL) and cyclohexane (30 mL) was added trifluoromethanesulfonic acid (0.04 mL, 0.45 mmol) at 0° C. The reaction mixture was stirred for 56 h at ambient temperature and quenched by addition of saturated sodium bicarbonate solution (10 mL), and then diluted with methylene chloride (100 mL). The organic layer was separated and washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol afforded 1-((4-bromo-2-chloro-5-fluorobenzyl)-oxy)adamantane as a colorless solid (0.70 g, 43%): 1H NMR (300 MHz, CDCl3) δ 7.47 (d, J=6.3 Hz, 1H), 7.37 (d, J=9.3 Hz, 1H), 4.48 (s, 2H), 2.16 (br s, 3H), 1.82-1.80 (m, 6H), 1.70-1.55 (m, 6H).

Workup

  1. customquenched by addition of saturated sodium bicarbonate solution (10 mL)
  2. additiondiluted with methylene chloride (100 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue
  8. customby column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol

Sources & evidence

ORD record
ord-f5908e551c114a48aee683d5c1e612ee
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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