2,6-Lutidine → (2-(3,5-Difluorophenyl)propan-2-yloxy)triisopropylsilane

HRID 705187

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:9]([OH:12])([CH3:11])[CH3:10])[CH:5]=[C:6]([F:8])[CH:7]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:27]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])[CH3:29])(=O)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C:9]([O:12][Si:27]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])[CH3:29])([CH3:10])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 1-(3,5-difluorophenyl)ethanone (1.0 equiv) in THF (0.2 M) at 0° C. was added methylmagnesium bromide (1.0 M in THF, 1.15 equiv). After stirring for 4 hours the reaction was quenched by addition of NH4Cl(sat), diluted with EtOAc, washed with NaCl(sat), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield 2-(3,5-difluorophenyl)propan-2-ol. To a solution of 2-(3,5-difluorophenyl)propan-2-ol in CH2Cl2 (0.1 M) at 0° C. was added 2,6 lutidine (6 equiv.) and than triisopropylsilyl trifluoromethanesulfonate (3.0 equiv.). After stirring for 3 hours at 0° C. and six hours at rt the solution was partitioned between EtOAc and NaHCO3(sat), separated, washed with NaCl(sat), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield (2-(3,5-difluorophenyl)propan-2-yloxy)triisopropylsilane. (400 MHz, <cdcl3>) δ ppm 1.05-1.08 (m, 21 H) 1.57 (s, 6 H) 6.63 (s, 1 H) 7.00 (dd, J=9.39, 2.35 Hz, 2 H).

Workup

customwas partitioned between EtOAc and NaHCO3(sat)
customseparated
washwashed with NaCl(sat)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
custompurified by ISCO SiO2 chromatography

Sources & evidence

ORD record: ord-fad4e449185345eeb3ae1de468774398
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09173883B2

Linked notes

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