4-[((1S)-2-(benzyloxy)-1-{[(triisopropylsilyl)oxy]methyl}ethyl)oxy]-4'-(trifluoromethoxy)-1,1'-biphenyl → (2S)-2-{[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl)oxy}-3-[(triisopropylsilyl)oxy]-1-propanol

HRID 1496909Notes

Reaction equation

HRID 1496909 reaction equation
C([O:8][CH2:9][C@H:10]([O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=2)=[CH:26][CH:25]=1)[CH2:11][O:12][Si:13]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])C1C=CC=CC=1>[Pd].CCOC(C)=O.CCO>[F:40][C:37]([F:38])([F:39])[O:36][C:33]1[CH:32]=[CH:31][C:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][C@H:10]([CH2:11][O:12][Si:13]([CH:17]([CH3:19])[CH3:18])([CH:20]([CH3:21])[CH3:22])[CH:14]([CH3:16])[CH3:15])[CH2:9][OH:8])=[CH:25][CH:26]=2)=[CH:35][CH:34]=1

Participants

4

Reactant 1

HCID 547569974-[((1S)-2-(benzyloxy)-1-{[(triisopropylsilyl)oxy]methyl}ethyl)oxy]-4'-(trifluoromethoxy)-1,1'-biphenyl

Product 1

HCID 54756998(2S)-2-{[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl)oxy}-3-[(triisopropylsilyl)oxy]-1-propanol

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21584252Ethanol ethylacetateSolvent

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. customThe catalyst was removed by filtration through Celite
  2. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1c9ab656030741c0b867fa83e1949b1e
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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