Water → HCID 70995998, compound

HRID 626941Notes

Reaction equation

HRID 626941 reaction equation
[H-].[Na+].C(OP([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[C:18]1([CH:24]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:25]2[CH2:28][C:27](=O)[CH2:26]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O>C1COCC1>[C:18]1([CH:24]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:25]2[CH2:28][C:27](=[C:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:26]2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 107155Triethyl 2-phosphonopropionateHCID 37355581-(Diphenylmethyl)azetidin-3-one

Product 1

HCID 70995998HCID 70995998, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60%, 202 mg, 5.06 mmol) was suspended in anhydrous THF (15 mL) and cooled in an ice bath. Ethyl 2-(diethoxyphosphoryl)propanoate (1.2 g, 5.06 mmol) was added dropwise under nitrogen and the mixture was stirred in an ice bath for 1 h. 1-(Diphenylmethyl)azetidin-3-one (1 g, 4.21 mmol) was added in portions as a solid and the mixture was stirred at room temperature for 1 h, then left to stir at room temperature overnight. Water (50 mL) was added and the mixture was extracted with DCM (3×50 mL). Brine was added, and the aqueous and organic layers were separated. The organic layer was dried over sodium sulfate and concentrated. The resulting crude yellow oil was purified by FCC, eluting with 0-50% EtOAc, to afford a clear oil which crystallised upon standing. The solids were sonicated with heptane and the remaining solid was collected by filtration. The filtrate was concentrated and sonicated with heptane to afford a second crop of solid. The filtrate was concentrated and the residue was sonicated with heptane to afford a further crop of solid material. The resultant solids were collected and combined to afford the title compound (892 mg, 66%) as a white solid. δH (250 MHz, CDCl3) 7.56-7.39 (m, 4H), 7.38-7.15 (m, 6H), 4.63-4.45 (m, 1H), 4.24-4.01 (m, 4H), 3.96-3.76 (m, 2H), 1.72-1.58 (m, 3H), 1.27-1.14 (m, 3H).

Workup

  1. temperaturecooled in an ice bath
  2. stirringthe mixture was stirred at room temperature for 1 h
  3. waitleft
  4. stirringto stir at room temperature overnight
  5. extractionthe mixture was extracted with DCM (3×50 mL)
  6. additionBrine was added
  7. customthe aqueous and organic layers were separated
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe resulting crude yellow oil was purified by FCC
  11. washeluting with 0-50% EtOAc
  12. customto afford a clear oil which
  13. customcrystallised
  14. customThe solids were sonicated with heptane
  15. filtrationthe remaining solid was collected by filtration
  16. concentrationThe filtrate was concentrated
  17. customsonicated with heptane
  18. customto afford a second crop of solid
  19. concentrationThe filtrate was concentrated
  20. customthe residue was sonicated with heptane
  21. customto afford a further crop of solid material
  22. customThe resultant solids were collected

Sources & evidence

ORD record
ord-9243bc6d8e0b41f8b917af834b6ed680
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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