Carbon tetrabromide → (S)-2-bromomethyl-1-(cyclohexyl-methoxy-methyl)-4-trifluoromethyl-benzene

HRID 2075026Notes

Reaction equation

HRID 2075026 reaction equation
[CH:1]1([C@H:7]([O:20][CH3:21])[C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=2[CH2:18]O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Br)(Br)(Br)[Br:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:23][CH2:18][C:9]1[CH:10]=[C:11]([C:14]([F:17])([F:16])[F:15])[CH:12]=[CH:13][C:8]=1[C@H:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[O:20][CH3:21]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58968688(S)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-phenyl]-methanol

Product 1

HCID 58968737(S)-2-bromomethyl-1-(cyclohexyl-methoxy-methyl)-4-trifluoromethyl-benzeneYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-phenyl]-methanol (340 mg, 1.2 mmol) in methylene chloride (10 mL) at 0° C. was added carbon tetrabromide (485 mg, 1.46 mmol) and stirred for 10 minutes followed by addition of triphenylphosphine (383 mg, 1.46 mmol). Reaction was stirred at 0° C. for 1 hour and allowed to warm to room temperature and stirred for 16 hours. Reaction was concentrated in vacuo and purified on 25+S Biotage column eluting with 0-20% ethyl acetate in heptane (10 CV), 20% (2CV), to yield the title compound (270 mg, 66%) as a colorless oil. This oil solidified upon standing and was recrystalized from hexane to yield crystals (mp=43-45° C.), which were submitted to X-ray crystallography to establish absolute configuration. 1H NMR (400 MHz, CDCl3) δ ppm 1.1 (m, 4H) 1.3 (m, 2H) 1.6 (m, 3H) 1.7 (m, 1H) 2.0 (d, J=12.6, 1H) 3.2 (s, 3H) 4.2 (d, J=7.9, 1H) 4.5 (d, J=10.3 Hz, 1H) 4.6 (d, J=10.3 Hz, 1H) 7.4 (d, J=8.3 Hz, 1H) 7.5 (d, J=8.3 Hz, 1H) 7.6 (s, 1H). [α]D20=−50 deg (c=11.5 mg/mL, acetone)

Workup

  1. customReaction
  2. stirringwas stirred at 0° C. for 1 hour
  3. stirringstirred for 16 hours
  4. customReaction
  5. concentrationwas concentrated in vacuo
  6. custompurified on 25+S Biotage column
  7. washeluting with 0-20% ethyl acetate in heptane (10 CV), 20% (2CV)

Sources & evidence

ORD record
ord-e6a4a024b35549d89af073880f5d5e14
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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