Tetrahydrofuran → HCID 86643813, compound

HRID 1929306Notes

Reaction equation

HRID 1929306 reaction equation
[CH3:1][N:2]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][CH2:4][C:3]1=[O:15].O1CCCC1.[N:21](OCCC(C)C)=[O:22].CC(C)([O-])C.[K+]>Cl.C(OC)(C)(C)C.C1CCCCC1>[CH3:1][N:2]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:4](=[N:21][OH:22])[C:3]1=[O:15]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 8053Isoamyl NitriteHCID 19881570HCID 19881570, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 86643813HCID 86643813, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8078CyclohexaneSolvent2×HCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
-10 °C

Procedure

The 1-methyl-5-phenyl-1,3-dihydro-azepin-2-one (183 g, 918.4 mmol) is combined with tetrahydrofuran (1500 mL) and the solution cooled to −25° C. to −30° C. Isoamyl nitrite (148.1 mL, 1.102 mol) is added followed by potassium tertiary-butoxide (108.2 g, 964.4 mmol) providing an exotherm to about −5° C. The solution is re-cooled to −10° C., then allowed to slowly warm to room temperature. The reaction contents are allowed to stir overnight. The reaction contents are diluted with 3N aqueous HCl (300 mL) providing a pH of about 2. It is then diluted with methyl tertiary-butyl ether (4 L) and washed the contents with 0.5-1.0 N HCl (2×600 mL) and saturated aqueous sodium chloride. The dark organic layer is dried over MgSO4, filtered, and concentrated to provide a residue wet with tetrahydrofuran. The residue is diluted with cyclohexane (300 mL) and concentrated to provide about 275 g of a crude residue that is slurried in methyl tertiary-butyl ether (450 mL) and cyclohexane (1000 mL). Heat the slurry to about 40° C., cool to room temperature, filter, and rinse with cyclohexane. Vacuum dry at 40° C. to provide the title compound (169 g, 81%) as a brown powder.

Workup

  1. temperaturethe solution cooled to −25° C. to −30° C
  2. customproviding an exotherm to about −5° C
  3. temperatureto slowly warm to room temperature
  4. customThe reaction contents
  5. customThe reaction contents
  6. customproviding a pH of about 2
  7. washwashed the contents with 0.5-1.0 N HCl (2×600 mL) and saturated aqueous sodium chloride
  8. dry with materialThe dark organic layer is dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide a residue wet with tetrahydrofuran
  12. concentrationconcentrated
  13. customto provide about 275 g of a crude residue that
  14. temperatureHeat the slurry to about 40° C.
  15. temperaturecool to room temperature
  16. filtrationfilter
  17. washrinse with cyclohexane
  18. customVacuum dry at 40° C.

Sources & evidence

ORD record
ord-2c165b6e8b6a4eddbc20db0f25555cba
Source dataset
uspto-grants-2012_05
Patent number
US08188069B2

Reaction notes

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