HCID 18472642, compound → HCID 18472426, compound

HRID 2228296Notes

Reaction equation

HRID 2228296 reaction equation
C([Li])CCC.CO[C:8]([C:10]1[CH:24]=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:22]=[CH:21][C:11]=1[O:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:9]>C1COCC1.C(NC(C)C)(C)C>[O:28]1[CH2:27][CH2:26][N:25]([C:23]2[CH:22]=[CH:21][C:11]3[O:12][CH2:13][CH2:14][CH:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:8](=[O:9])[C:10]=3[CH:24]=2)[CH2:30][CH2:29]1

Participants

5

Reactant 2

HCID 18472642HCID 18472642, compoundHCID 178418339Butyllithium

Product 1

HCID 18472426HCID 18472426, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 7912DiisopropylamineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In THF (15 ml) was dissolved diisopropylamine (1.018 ml), and to the mixture was added dropwise at 0° C. n-butyl lithium (4.2 ml). The mixture was stirred at the same temperature for 30 minutes. To the mixture was added dropwise a solution of ethyl 4-(2-methoxycarbonyl-4-morpholinophenoxy)butyrate (1829 mg, 5.18 mmol) in THF (5 ml) at −78° C., ice bath was removed, and the mixture was stirred for 7 hours. To the mixture was added at 0° C. 10% ammonium chloride solution (30 ml), and the mixture was extracted with ethyl acetate (30 ml×3). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified with column chromatography (silica gel 50 g, ethyl acetate/hexane=1/5), and the desired fraction was concentrated under reduced pressure to give ethyl 7-morpholino-5-oxo-2,3,4,5-tetrahydro-1-benzoxepine-4-carboxylate (924 mg, 2.89 mmol, 56%).

Workup

  1. customice bath was removed
  2. stirringthe mixture was stirred for 7 hours
  3. additionTo the mixture was added at 0° C
  4. extraction10% ammonium chloride solution (30 ml), and the mixture was extracted with ethyl acetate (30 ml×3)
  5. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified with column chromatography (silica gel 50 g, ethyl acetate/hexane=1/5)
  8. concentrationthe desired fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-af8f103252904526aeb017d33ab881be
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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