4-(5-Fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanal → 1-(3,5-Dimethylphenyl)-5-(5-fluoro-2-methoxyphenyl)-3-methoxymethoxy-5-methyl-3-trifluoromethylhexan-2-ol

HRID 916014Notes

Reaction equation

HRID 916014 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([C:8]([CH3:22])([CH3:21])[CH2:9][C:10]([O:17][CH2:18][O:19][CH3:20])([C:13]([F:16])([F:15])[F:14])[CH:11]=[O:12])[CH:7]=1.[CH3:25][C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([CH3:35])[CH:34]=1)[CH2:29][Mg]Br>C1COCC1>[CH3:25][C:26]1[CH:34]=[C:33]([CH2:35][CH:11]([OH:12])[C:10]([O:17][CH2:18][O:19][CH3:20])([C:13]([F:16])([F:15])[F:14])[CH2:9][C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:23][CH3:24])([CH3:21])[CH3:22])[CH:32]=[C:28]([CH3:29])[CH:27]=1

Participants

4

Reactant 2

HCID 589600374-(5-Fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanalHCID 178424986HCID 178424986, compound

Product 1

HCID 589599681-(3,5-Dimethylphenyl)-5-(5-fluoro-2-methoxyphenyl)-3-methoxymethoxy-5-methyl-3-trifluoromethylhexan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 398 mg (1.1 mmol) of the above 4-(5-fluoro-2-methoxyphenyl)-2-methoxymethoxy-4-methyl-2-trifluoromethylpentanal in 4 mL of anhydrous THF, 10 mL (2.5 mmol) of a 0.25 M solution of 3,5-dimethylbenzylmagnesium bromide in THF was added. The mixture stirred for 4 hours and was then quenched with 10 mL of saturated ammonium chloride and extracted with three 10 mL portions of EtOAc. The combined organic layers were washed with three 5 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The mixture of diastereomers was purified by chromatography on silica gel eluting with dichloromethane-hexanes (0:100, then 10:90, then 15:85, then 20:80, then 25:75, then 3:7, then 4:6) to afford first 121 mg (22%) of a single diastereomer of 1-(3,5-dimethylphenyl)-5-(5-fluoro-2-methoxyphenyl)-3-methoxymethoxy-5-methyl-3-trifluoromethylhexan-2-ol, and then 137 mg (25%) of the second diastereomer.

Workup

  1. customwas then quenched with 10 mL of saturated ammonium chloride
  2. extractionextracted with three 10 mL portions of EtOAc
  3. washThe combined organic layers were washed with three 5 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe mixture of diastereomers
  8. customwas purified by chromatography on silica gel eluting with dichloromethane-hexanes (0:100

Sources & evidence

ORD record
ord-433dee42ae094830be40b8c452e9d60a
Source dataset
uspto-grants-2007_09
Patent number
US07268152B2

Reaction notes

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