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

HRID 1496910
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HRID 1496910 반응식
[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]
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참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 241Benzene용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-49f1bba4309648b29353b37ca5231f3d
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09198913B2

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