(R)-2-Methyl-CBS-oxazaborolidine → 2-Hydroxyquinoline

HRID 493419Notes

Reaction equation

HRID 493419 reaction equation
C1(CO[C:9]2[CH:10]=[CH:11][C:12](C(=O)CCl)=[C:13]3[C:18]=2[NH:17][C:16](=[O:19])[CH:15]=[CH:14]3)C=CC=CC=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1>C1(C)C=CC=CC=1.C1COCC1>[NH:17]1[C:18]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:14]=[CH:15][C:16]1=[O:19]

Participants

5

Reactant 2

HCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 109035505-(2-chloroacetyl)-8-phenylmethoxy-1H-quinolin-2-one

Product 1

HCID 60382-Hydroxyquinoline

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
1 °C

Procedure

A dry 3 L, 4-necked flask equipped with a mechanical stirrer, thermometer, addition funnel and refluxing condenser is charged with 50 g 8-(phenylmethoxy)-5-(α-chloroacetyl)-(1H)-quinolin-2-one and 600 mL dry THF under N2. Then 15 mL of a 1 molar solution of (R)-tetrahydro-1-methyl-3,3-diphenyl-(1H,3H)-pyrrolo[1,2-c][1,3,2]-oxazaborole in toluene was added. The mixture was cooled to an internal temperature of 0-2° C. and while maintaining an internal temperature of 0-2° C., 153 mL of a 1 molar solution of BH3 in THF was added over 1-2 hours. The reaction was stirred for another hour at an internal temperature of 0-2° C. and then quenched by addition of 65 mL methanol. The resulting solution was warmed to 25° C. and concentrated to a volume of 250 mL (50° C./200 mbar). To this concentrate was added a mixture of 713 mL water and 37 g HCl 37%. During the addition 8-(phenylmethoxy)-5-((R)-2-chloro-1-hydroxy-ethyl)-(1H)-quinolin-2-one precipitated as a nearly colourless precipitation. The resulting suspension was stirred for 30 minutes at 25° C., filtrated and washed with 220 mL water in several portions. Drying in a vacuum drier at 50° C. for 12 hours resulted in 47.41 g of 8-(phenylmethoxy)-5-((R)-2-chloro-1-hydroxy-ethyl)-(1H-quinolin-2-one as a slightly yellowish powder.

Workup

  1. customA dry 3 L, 4-necked flask equipped with a mechanical stirrer
  2. additionthermometer, addition funnel
  3. temperaturerefluxing condenser
  4. additionwas added over 1-2 hours
  5. customquenched by addition of 65 mL methanol
  6. temperatureThe resulting solution was warmed to 25° C.
  7. concentrationconcentrated to a volume of 250 mL (50° C./200 mbar)
  8. additionTo this concentrate was added
  9. additiona mixture of 713 mL water and 37 g HCl 37%
  10. additionDuring the addition 8-(phenylmethoxy)-5-((R)-2-chloro-1-hydroxy-ethyl)-(1H)-quinolin-2-one
  11. customprecipitated as a nearly colourless precipitation
  12. stirringThe resulting suspension was stirred for 30 minutes at 25° C.
  13. filtrationfiltrated
  14. washwashed with 220 mL water in several portions
  15. customDrying in a vacuum drier at 50° C. for 12 hours

Sources & evidence

ORD record
ord-8cb76f23a3f449f788f939c77ced409d
Source dataset
uspto-grants-2009_05
Patent number
US07534890B2

Reaction notes

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