Acetic Acid → Diisopropyl Ether

HRID 2243341Notes

Reaction equation

HRID 2243341 reaction equation
[Cl:1][C:2]1[C:3]([F:26])=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[C:22]4[C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[C:15](=[N:23]O)[C:14]=4[CH:13]=[CH:12][CH:11]=3)[NH:7][C:6]=2[CH:25]=1.[C:27]([OH:30])(=O)[CH3:28].[CH2:31](O)C>O.[Zn]>[CH:27]([O:30][CH:22]([CH3:21])[CH3:10])([CH3:28])[CH3:31].[Cl:1][C:2]1[C:3]([F:26])=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[C:22]4[C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[CH:15]([NH2:23])[C:14]=4[CH:13]=[CH:12][CH:11]=3)[NH:7][C:6]=2[CH:25]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 178526306HCID 178526306, compound

Product 2

HCID 7914Diisopropyl EtherHCID 178507135HCID 178507135, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Procedure

The procedure used in Example 216 is followed. In a 100 ml round-bottomed flask under an argon atmosphere, dissolve 1.1 g of 4-(6-chloro-5-fluoro-1H-benzimidazol-2-yl)-9H-fluoren-9-one oxime (Z,E), obtained in the previous stage, in a mixture of 6.7 ml of ethanol and 6.7 ml of water and 6.7 ml of acetic acid, at room temperature, add 782 mg of zinc in three stages, and, between each addition, stir for approximately one to two hours. Add Celite and filter. The filtrate is concentrated under pressure. The crude product is purified by flash chromatography on silica gel (40-63 μm), eluting with a mixture of dichloromethane and ammonia as a 7N solution in methanol (9/1 by volume). After formation of a paste with diisopropyl ether, in this way we obtain 860 mg of 4-(6-chloro-5-fluoro-1H-benzimidazol-2-yl)-9H-fluorene-9(R,S)-amine, in the form of an off-white powder, which is used as it is in the following stage, with the following characteristics:

Workup

  1. additionbetween each addition
  2. filtrationAdd Celite and filter
  3. concentrationThe filtrate is concentrated under pressure
  4. customThe crude product is purified by flash chromatography on silica gel (40-63 μm)
  5. washeluting with a mixture of dichloromethane and ammonia as a 7N solution in methanol (9/1 by volume)

Sources & evidence

ORD record
ord-5ce9607dafbc40d890cb83b9a373949a
Source dataset
uspto-grants-2010_03
Patent number
US07674795B2

Reaction notes

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