Formic Acid → 4-[4-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-2,6-dimethylpiperazine-1-carbaldehyde

HRID 2105989Notes

Reaction equation

HRID 2105989 reaction equation
[CH3:1][CH:2]1[NH:7][CH:6]([CH3:8])[CH2:5][N:4]([CH2:9][C:10]([OH:28])([CH2:15][C:16]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[O:26][CH3:27])([CH3:18])[CH3:17])[C:11]([F:14])([F:13])[F:12])[CH2:3]1.[CH:29](OC=O)=[O:30].C(N=C=NC(C)C)(C)C.C(O)=O>C(Cl)Cl.N1C=CC=CC=1>[F:25][C:23]1[CH:22]=[CH:21][C:20]([O:26][CH3:27])=[C:19]([C:16]([CH3:18])([CH3:17])[CH2:15][C:10]([OH:28])([C:11]([F:12])([F:13])[F:14])[CH2:9][N:4]2[CH2:3][CH:2]([CH3:1])[N:7]([CH:29]=[O:30])[CH:6]([CH3:8])[CH2:5]2)[CH:24]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 12734DiisopropylcarbodiimideHCID 9548680Formic anhydride2×HCID 57809802HCID 57809802, compound

Product 1

HCID 103428654-[4-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-2,6-dimethylpiperazine-1-carbaldehyde

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(3,5-dimethylpiperazin-1-ylmethyl)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-ol (20 mg) in methylene chloride (1 mL) at 0° C. was added pyridine (60.7 μL) followed by formic anhydride (2M in methylene chloride, 0.5 mL). (Formic anhydride was freshly prepared by slow addition of one equivalent of 1,3-diisopropylcarbodiimide to 2 equivalents of formic acid in methylene chloride. The resulting suspension was stirred for 1 hour, and filtered). The resulting mixture was stirred overnight for 20 hours, filtered through a cotton plug, poured into half-saturated aqueous sodium bicarbonate solution, and extracted twice with methylene chloride. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluted with 5% methanol-methylene chloride) to give the title compound as a clear oil (19.3 mg).

Workup

  1. filtrationfiltered)
  2. stirringThe resulting mixture was stirred overnight for 20 hours
  3. filtrationfiltered through a cotton plug
  4. additionpoured into half-saturated aqueous sodium bicarbonate solution
  5. extractionextracted twice with methylene chloride
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel (eluted with 5% methanol-methylene chloride)

Sources & evidence

ORD record
ord-370790d94eb9424484f8c5e28901e465
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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