Imidazole → 4-[((1R)-2-iodo-1-{[(triisopropylsilyl)oxy]methyl}ethyl)oxy]-4'-(trifluoromethoxy)-1,1'-biphenyl

HRID 1496910Notes

Reaction equation

HRID 1496910 reaction equation
[I:1]I.[F:3][C:4]([F:35])([F:34])[O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][C@H:19]([CH2:22][O:23][Si:24]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[CH:25]([CH3:27])[CH3:26])[CH2:20]O)=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1>C1C=CC=CC=1>[I:1][CH2:20][C@H:19]([O:18][C:15]1[CH:16]=[CH:17][C:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][C:4]([F:35])([F:34])[F:3])=[CH:7][CH:8]=2)=[CH:13][CH:14]=1)[CH2:22][O:23][Si:24]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[CH:25]([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 54756998(2S)-2-{[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl)oxy}-3-[(triisopropylsilyl)oxy]-1-propanol

Product 1

HCID 547569994-[((1R)-2-iodo-1-{[(triisopropylsilyl)oxy]methyl}ethyl)oxy]-4'-(trifluoromethoxy)-1,1'-biphenylYield 81%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of the benzyl ether 80 (10.79 g, 0.019 mol) and 5% Pd—C (500 mg) in 1:1 EtOAc/EtOH (250 mL) was hydrogenated at 60 psi for 4 h. The catalyst was removed by filtration through Celite and the filtrate was concentrated under reduced pressure to give (2S)-2-{[4′-(trifluoromethoxy)[1,1′-biphenyl]-4-yl]oxy}-3-[(triisopropylsilyl)oxy]-1-propanol (81) as a viscous oil, sufficiently pure for use in the next step. Iodine (6.03 g, 0.024 mol) was added in portions at 20° C. to a vigorously stirred solution of the crude alcohol 81, triphenylphosphine (6.23 g, 0.024 mol) and imidazole (2.49 g, 0.036 mol) in benzene (100 mL) and stirring was continued for 1 h. After dilution with EtOAc the mixture was washed with water, 2N Na2SO3 and water again. The extract was evaporated and chromatographed on silica gel, eluting with EtOAc/petroleum ether (1:19), to give 4-[((1R)-2-iodo-1-{[(triisopropylsilyl)oxy]methyl}ethyl)oxy]-4′-(trifluoromethoxy)-1,1′-biphenyl (82) (9.08 g, 81% overall) as a colourless oil; 1H NMR (CDCl3) δ 7.54 (d, J=8.8 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 7.26 (br d, J=8.8 Hz, 2H), 7.02 (d, J=8.8 Hz, 2H), 4.31-4.25 (m, 1H), 4.03 (dd, J=10.4, 4.8 Hz, 1H), 3.93 (dd, J=10.4, 5.6 Hz, 1H), 3.55 (dd, J=10.5, 5.6 Hz, 1H), 3.45 (dd, J=10.5, 4.8 Hz, 1H), 1.15-1.06 (m, 21H). APCI MS m/z 595 [M+H]+.

Workup

  1. washAfter dilution with EtOAc the mixture was washed with water, 2N Na2SO3 and water again
  2. customThe extract was evaporated
  3. customchromatographed on silica gel
  4. washeluting with EtOAc/petroleum ether (1:19)

Sources & evidence

ORD record
ord-49f1bba4309648b29353b37ca5231f3d
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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