Water → HCID 18472369, compound

HRID 1277285Notes

Reaction equation

HRID 1277285 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[CH:9][C:10]3[O:16][CH2:15][CH2:14][CH:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12](=O)[C:11]=3[CH:23]=2)[CH2:3][CH2:2]1.[BH4-].[Na+].O.C(N(CC)CC)C>C1COCC1.CO>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[CH:8]=[CH:9][C:10]3[O:16][CH2:15][CH2:14][C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][C:11]=3[CH:23]=2)[CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 18472426HCID 18472426, compound

Product 1

HCID 18472369HCID 18472369, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

In THF (10 ml) was dissolved ethyl 7-morpholino-5-oxo-2,3,4,5-tetrahydro-1-benzoxepine-4-carboxylate (924 mg, 2.89 mmol), and to the mixture was added at -30° C. a solution of sodium boro hydride (164 mg, 4.34 mmol) in methanol (3 ml). The mixture was stirred at -20° C. to -15° C. for 30 minutes, and the mixture was cooled to -50° C., to which was added water (15 ml). The mixture was extracted with ethylacetate (15 ml×3), and the organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in THF (10 ml), and to the mixture were added at 0° C. triethylamine (2.02 ml, 14.5 mmol) andmethanesulfonylchloride (0.336 ml, 4.34 mmol). The mixture was stirred at room temperature for 17 hours and concentrated under reduced pressure. To the residue was added water (15 ml), and the mixture was extracted with ethyl acetate (20 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 30 g, ethyl acetate/ hexane=1/5), and the desired fraction was concentrated under reduced pressure to give ethyl 7-morpholino-2,3-dihydro-1-benzoxepine-4-carboxylate (691 mg, 2.28 mmol, 79%).

Workup

  1. extractionThe mixture was extracted with ethylacetate (15 ml×3)
  2. dry with materialthe organic layer was dried with anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in THF (10 ml)
  5. stirringThe mixture was stirred at room temperature for 17 hours
  6. concentrationconcentrated under reduced pressure
  7. additionTo the residue was added water (15 ml)
  8. extractionthe mixture was extracted with ethyl acetate (20 ml×3)
  9. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified with column chromatography (silica gel 30 g, ethyl acetate/ hexane=1/5)
  12. concentrationthe desired fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-4d258decd1d944a79439a97971a81124
Source dataset
uspto-grants-2000_12
Patent number
US06166006

Reaction notes

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