Tetrahydrofuran → HCID 66712780, compound

HRID 1406161Notes

Reaction equation

HRID 1406161 reaction equation
C(O[C:4](=[O:37])[C:5]1[CH:10]=CC(OC2C=CC=CC=2)=[CH:7][C:6]=1[CH2:18][N:19]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=1[O:35][CH3:36])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+].[CH2:50]1[CH2:54][O:53][CH2:52][CH2:51]1>>[CH2:24]([O:23][C:21]([C:20]1[N:19]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])[CH2:18][C:6]2[C:5]([C:4]=1[OH:37])=[CH:10][CH:50]=[C:54]([O:53][C:52]1[CH:51]=[CH:7][CH:6]=[CH:5][CH:4]=1)[CH:7]=2)=[O:22])[CH3:25]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 66713386HCID 66713386, compound

Product 1

HCID 66712780HCID 66712780, compound

Procedure

460 mg of 2-{[(2,4-Dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-4-phenoxy-benzoic acid ethyl ester was dissolved in 16 mL of anhydrous THF and the resultant solution cooled to −78 deg C. under a nitrogen atmosphere. To the solution was added 1.95 mL of 1.0 M lithium bis(trimethylsilyl) amide in THF. The reaction was stirred at −78 deg C. for 1.5 h, and at room temperature for 4.5 hours. The resultant solution was poured into a solution of saturated aqueous ammonium chloride and extracted three times with ethyl acetate. The organic fractions were washed with brine, dried over anhydrous sodium sulfate and concentrated to yellow oil. The oil was flash columned on silica gel, eluting with a gradient of 20-75% ethyl acetate in hexanes. The eluted fractions were concentrated under reduced pressure to 373 mg of a yellow oil, which was determined to be a mixture of the enol and keto tautomers of the desired product; MS (+) m/z 484.20 (m+23).

Workup

  1. waitat room temperature for 4.5 hours
  2. extractionextracted three times with ethyl acetate
  3. washThe organic fractions were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated to yellow oil
  6. washeluting with a gradient of 20-75% ethyl acetate in hexanes
  7. concentrationThe eluted fractions were concentrated under reduced pressure to 373 mg of a yellow oil, which
  8. additiona mixture of the enol and keto tautomers of the desired product

Sources & evidence

ORD record
ord-af5326cd7d0c4ecfb8651cc2ccabfd76
Source dataset
uspto-grants-2014_12
Patent number
US08916585B2

Reaction notes

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