Water → Oxirane, ((phenylmethoxy)methyl)-, (S)- (9CI)

HRID 1261400Notes

Reaction equation

HRID 1261400 reaction equation
[H-].[Na+].[CH2:3]1[O:5][CH:4]1[CH2:6][OH:7].[CH2:8](Cl)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.O>CN(C=O)C.[Na+].[I-]>[CH2:8]([O:7][CH2:6][C@@H:4]1[CH2:3][O:5]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7503Benzyl Chloride2×HCID 11164GlycidolHCID 24758Sodium hydride

Product 1

HCID 146296Oxirane, ((phenylmethoxy)methyl)-, (S)- (9CI)Yield 78.6%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6228DimethylformamideSolvent3×

Procedure

A slurry of NaH (267 g) and NaI (26.5 g) in DMF (3000 mL) was cooled to between −15° C. and −10° C. with ice-brine mixture. A solution of glycidol (480 g) in DMF (1000 mL) was added with stirring for 10 minutes. BnCl (745.5 g) in DMF (800 mL) was added (slightly exothermic) and the reaction was warmed to room temperature followed by stirring for approximately 16 hours. The solution was stirred for a further time period until HPLC analysis showed less than 1% of BnCl remained. The reaction was cooled to −5° C. and water (4 L) was added. MBTE (5 L) was added with stirring for 30 minutes. The organic and aqueous layers were separated and two additions of MBTE (5 L; 3.5 L) were used to extract the aqueous layer. The combined organic layer was washed with brine (1.8 L (×2)) and dried over Na2SO4 for 1 hour. The organic layer was concentrated to dryness, distilled under vacuum (5 mm Hg, 85° C.) to give the product as a yellow liquid (760 g). 1H NMR (CDCl3, 400 MHz): δ 7.27-7.37 (m, 5H), 4.51 (s, 2H), 3.74 (dd, 1H), 3.29 (dd, 1H), 3.14 (m, 1H), 2.72 (dd, 1H), 2.55 (dd, 1H).

Workup

  1. stirringby stirring for approximately 16 hours
  2. stirringThe solution was stirred for a further time period until HPLC analysis
  3. temperatureThe reaction was cooled to −5° C.
  4. additionMBTE (5 L) was added
  5. stirringwith stirring for 30 minutes
  6. customThe organic and aqueous layers were separated
  7. extractionto extract the aqueous layer
  8. washThe combined organic layer was washed with brine (1.8 L (×2))
  9. dry with materialdried over Na2SO4 for 1 hour
  10. concentrationThe organic layer was concentrated to dryness
  11. distillationdistilled under vacuum (5 mm Hg, 85° C.)

Sources & evidence

ORD record
ord-188cc38f529447ab87f525cf115799a5
Source dataset
uspto-grants-2013_06
Patent number
US08470878B2

Reaction notes

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