4-Chlorobenzaldehyde → HCID 12157976, compound

HRID 629767Notes

Reaction equation

HRID 629767 reaction equation
[O:1]=[C:2]([N:10]1[C@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][O:12][C:11]1=[O:21])[CH2:3]P(=O)(OC)OC.CC(C)([O-])C.[K+].[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][CH:30]=1>C1COCC1>[Cl:28][C:29]1[CH:36]=[CH:35][C:32](/[CH:33]=[CH:3]/[C:2]([N:10]2[C@H:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:13][O:12][C:11]2=[O:21])=[O:1])=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 23665647Potassium tert-butoxideHCID 86726375HCID 86726375, compound

Product 1

HCID 12157976HCID 12157976, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (R)-dimethyl 2-oxo-2-(2-oxo-4-phenyloxazolidin-3-yl)ethylphosphonate (60.7 g, 177.8 mmol) in dry THF (275 ml) under an atmosphere of N2 was cooled to 0° C. in an ice-water bath. Potassium tert-butoxide (23.9 g, 213.4 mmol, 1.0 M solution in THF) was added over a period of 45 min in a dropwise manner and the reaction mixture stirred at 0° C. for 30 min. A solution of 4-chlorobenzaldehyde (25.0 g, 177.84 mmol) in dry THF (100 ml) was added over a period of 20 min and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was cooled to 0° C. and quenched with saturated solution of ammonium chloride (250 mL) and diluted with EtOAc (1.5 L). The biphasic system was stirred at ambient temperature for 10 min and the layers were separated. The organic layer was washed with brine (250 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by SiO2 column using a gradient elution of 0-25% EtOAc in hexanes. Fractions containing product were combined and the solvents were removed in vacuo to provide the product (43.0 g, 74%) as a pale yellow solid.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 16 h
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with saturated solution of ammonium chloride (250 mL)
  4. additiondiluted with EtOAc (1.5 L)
  5. stirringThe biphasic system was stirred at ambient temperature for 10 min
  6. customthe layers were separated
  7. washThe organic layer was washed with brine (250 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by SiO2 column
  12. washa gradient elution of 0-25% EtOAc in hexanes
  13. additionFractions containing product
  14. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-066cf1545e3649509cfeb9d50a94beb1
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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