Diisobutylaluminum hydride → 3-(2-Chloro-4-hydroxymethyl-phenyl)-2-(2-chloro-pyridin-4-yl)-1,1,1-trifluoro-butan-2-ol
Reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([CH3:24])[C:11]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([Cl:23])[CH:18]=2)([OH:16])[C:12]([F:15])([F:14])[F:13])=[C:6]([Cl:25])[CH:5]=1.CC(C[AlH]CC(C)C)C>C(Cl)Cl>[Cl:25][C:6]1[CH:5]=[C:4]([CH2:3][OH:2])[CH:9]=[CH:8][C:7]=1[CH:10]([CH3:24])[C:11]([C:17]1[CH:22]=[CH:21][N:20]=[C:19]([Cl:23])[CH:18]=1)([OH:16])[C:12]([F:15])([F:14])[F:13]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -15 °C
Procedure
3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoic acid methyl ester (450 mg, obtained in Example 26, step 2) was dissolved in CH2Cl2 (10 mL) under argon. The solution was cooled to −15° C. in an ice/methanol bath and a solution of DIBAL-H (1M in CH2Cl2, 2.76 mL) was added dropwise. Stirring was continued and the mixture was allowed to warm to 0° C. over a period of 2 hours. The mixture was then poured into ice/water and extracted with ethyl acetate. The organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane) to give the title compound as a colorless foam (422 mg, 91%). MS (m/e)=380.1 [MH+].
Workup
- temperatureto warm to 0° C. over a period of 2 hours
- extractionextracted with ethyl acetate
- washThe organic extracts were washed with brine
- dry with materialdried over Na2SO4
- customevaporated
- customThe residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane)
Sources & evidence
- ORD record
- ord-eb337de232c94c3a86cd8dd9185ce73d
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08138189B2
Reaction notes
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