Diiodomethane → (4-((((1,1-Dimethylethyl)(dimethyl)silyl)oxy)methyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-2-yl)(1-methylcyclopropyl)methanol

HRID 1662533Notes

Reaction equation

HRID 1662533 reaction equation
[CH3:1][C:2]([Si:5]([CH3:29])([CH3:28])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=2[F:22])=[C:10]([CH:23]([OH:27])[C:24]([CH3:26])=[CH2:25])[CH:9]=1)([CH3:4])[CH3:3].I[CH2:31]I.C([Zn]CC)C>C(Cl)Cl>[CH3:4][C:2]([Si:5]([CH3:28])([CH3:29])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=2[F:22])=[C:10]([CH:23]([C:24]2([CH3:31])[CH2:26][CH2:25]2)[OH:27])[CH:9]=1)([CH3:1])[CH3:3]

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 577055531-(4-((((1,1-Dimethylethyl)(dimethyl)silyl)oxy)methyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-2-yl)-2-methyl-2-propen-1-olHCID 178418750HCID 178418750, compound

Product 1

HCID 57706611(4-((((1,1-Dimethylethyl)(dimethyl)silyl)oxy)methyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-2-yl)(1-methylcyclopropyl)methanolYield 85.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL round bottom flask was charged with 83.18D (0.92 g, 2.2 mmol), DCM (22 mL), and diiodomethane (available from Aldrich) (0.27 mL, 3.3 mmol) and cooled to 0° C. under N2. To the cold solution was added diethylzinc (1.0 M in heptane) (available from Aldrich) (3.3 mL, 3.3 mmol) at a rapid drip. The colorless mixture was stirred for 5 minutes. The cooling bath was removed, and the mixture was stirred for 2 hours at ambient temperature. The reaction was quenched with saturated aqueous NH4Cl and diluted with EtOAc. The organic phase was washed with 1 M Na2S2O3 and brine, dried (MgSO4), and concentrated. The residue was purified by silica gel flash chromatography (0-15% EtOAc/hexane) to afford 83.18E (0.81 g, 85%) as a colorless oil.

Workup

  1. customThe cooling bath was removed
  2. stirringthe mixture was stirred for 2 hours at ambient temperature
  3. customThe reaction was quenched with saturated aqueous NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with 1 M Na2S2O3 and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel flash chromatography (0-15% EtOAc/hexane)

Sources & evidence

ORD record
ord-6fe6884d2608459fa225a3e187761279
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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