Carbon tetrabromide → (S)-2-(bromomethyl)-1-(cyclopentyl(methoxy)methyl)-4-(trifluoro-methyl)benzene

HRID 2075035Notes

Reaction equation

HRID 2075035 reaction equation
[CH:1]1([CH:6]([O:19][CH3:20])[C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=2[CH2:17]O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Br)(Br)(Br)[Br:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:22][CH2:17][C:8]1[CH:9]=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=[CH:12][C:7]=1[C@H:6]([CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)[O:19][CH3:20]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58968669(2-(Cyclopentyl(methoxy)methyl)-5-(trifluoromethyl)phenyl)methanol

Product 1

HCID 58968705(S)-2-(bromomethyl)-1-(cyclopentyl(methoxy)methyl)-4-(trifluoro-methyl)benzeneYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2-(cyclopentyl(methoxy)methyl)-5-(trifluoromethyl)phenyl)methanol (enatiomer 2 from the chiral separation of the racemate in STEP C, 23.1 mg, 0.080 mmol) and carbon tetrabromide (34.5 mg, 0.10 mmol) in methylene chloride (0.5 mL) at room temperature was added triphenyl phosphine (27.3 mg, 0.10 mmol). The mixture was stirred at room temperature overnight. Solvent was removed and the residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-20-30% ethyl acetate in heptane) to afford the title compound (23.1 mg, 82%). 1H NMR (400 MHz, CDCl3) δ ppm 1.15-1.27 (m, 1H) 1.34-1.44 (m, 1H) 1.44-1.72 (m, 5H) 1.78-1.87 (m, 1H) 2.16-2.26 (m, 1H) 3.21 (s, 3H) 4.32 (d, J=7.88 Hz, 1H) 4.57 (d, J=10.37 Hz, 1H) 4.67 (d, J=10.37 Hz, 1H) 7.49-7.59 (m, 2H) 7.61 (s, 1H). The other enantiomer of the title compound was prepared in the same manner using enantiomer 1 from the chiral separation of the racemate in STEP C.

Workup

  1. customSolvent was removed
  2. customthe residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-20-30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8c9ad066981d4f31b0173c3cc0d430d3
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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