Tetrahydrofuran → HCID 57447696, compound

HRID 1669211Notes

Reaction equation

HRID 1669211 reaction equation
Cl.[CH3:2][O:3][CH:4]1[CH2:7][NH:6][CH2:5]1.BrCCC[C:12]12[CH:22]=[CH:21][CH:20]=[CH:19][CH:13]1[C:14]([NH:16][C:17]2=[O:18])=[O:15].C([O-])([O-])=O.[K+].[K+].[CH2:29]1[CH2:33]OC[CH2:30]1>>[CH3:2][O:3][CH:4]1[CH2:7][N:6]([CH2:30][CH2:29][CH2:33][N:16]2[C:14](=[O:15])[C:13]3[C:12](=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:17]2=[O:18])[CH2:5]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 18469342HCID 18469342, compoundHCID 222428583-Methoxyazetidine hydrochloride

Product 1

HCID 57447696HCID 57447696, compoundYield 65%

Procedure

A suspension of 3-methoxyazetidine (275) (MacKenzie et al., PCT Int. Appl. WO 9605193, 1996) (1.6 g, 18.8 mmol), 2-(3-bromopropyl)phthalimide (4.8 g, 17.9 mmol) and K2CO3 (3.7 g, 26.9 mmol) in THF (150 mL) was stirred at reflux temperature for 18 h. The solution was cooled, the solvent evaporated and the residue partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (2×150 mL), the combined organic fraction washed with water (2×100 mL) and brine (100 mL), dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-5%) of MeOH/DCM, to give phthalimide 300 (5.2 g, 65%) as a colourless oil: 1H NMR δ 7.84 (dd, J=5.4, 3.1 Hz, 2H, Harom), 7.70 (dd, J=5.4, 3.1 Hz, 2H, Harom), 3.95 (p, J=5.8 Hz, 1H, CHO), 3.73 (t, J=7.1 Hz, 2H, CH2N), 3.55-3.60 (m, 2H, CH2N), 3.22 (s, 3H, OCH3), 2.78-2.84 (m, 2H, CH2N), 2.51 (t, J=7.1 Hz, 2H, CH2N), 1.72 (p, J=7.1 Hz, 2H, CH2); MS (APCI) m/z 275 (MH+, 100%); HRMS (FAB+) calcd for C15H19N2O3 (MH+) m/z 275.1396, found 275.1391.

Workup

  1. temperatureat reflux temperature for 18 h
  2. temperatureThe solution was cooled
  3. customthe solvent evaporated
  4. customthe residue partitioned between water (50 mL) and EtOAc (100 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×150 mL)
  6. washthe combined organic fraction washed with water (2×100 mL) and brine (100 mL)
  7. customdried
  8. customthe solvent evaporated
  9. customThe residue was purified by chromatography
  10. washeluting with a gradient (0-5%) of MeOH/DCM

Sources & evidence

ORD record
ord-a2e26fd910514d56ab8c6c386316404d
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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