Water → 4-Cyclopropyl-5,7-difluoro-3,4-dihydro-2H-chromen-4-ol

HRID 561496Notes

Reaction equation

HRID 561496 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4](=[O:13])[CH2:5][CH2:6][O:7]2.[CH:14]1([Mg]Br)[CH2:16][CH2:15]1.O>C(OCC)C.O1CCCC1>[CH:14]1([C:4]2([OH:13])[C:3]3[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=3[F:1])[O:7][CH2:6][CH2:5]2)[CH2:16][CH2:15]1

Participants

6

Reactant 3

HCID 962WaterHCID 468354275,7-Difluorochroman-4-oneHCID 178418630HCID 178418630, compound

Product 1

HCID 583922924-Cyclopropyl-5,7-difluoro-3,4-dihydro-2H-chromen-4-ol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2.00 g (10.86 mmol) of the compound from Example 170A were dissolved in 40 ml of diethyl ether at 0° C., and 32.6 ml (16.29 mmol) of a 0.5N solution of cyclopropylmagnesium bromide in tetrahydrofuran were slowly added dropwise. Stirring at 0° C. for 1 h was followed by warming to RT, addition of water and diethyl ether to the reaction solution and separation of the phases. The aqueous phase was extracted with diethyl ether, and the combined organic phases were dried over sodium sulfate and filtered, and the solvents were removed in vacuo. The crude product was purified by preparative HPLC (mobile phase: acetonitrile/water gradient). The acetonitrile was removed from the combined product phases in a rotary evaporator, and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the solvents were removed in vacuo. 0.66 g (27% of theory) of the title compound was obtained.

Workup

  1. temperatureby warming to RT
  2. customto the reaction solution and separation of the phases
  3. extractionThe aqueous phase was extracted with diethyl ether
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvents were removed in vacuo
  7. customThe crude product was purified by preparative HPLC (mobile phase: acetonitrile/water gradient)
  8. customThe acetonitrile was removed from the combined product phases in a rotary evaporator
  9. extractionthe aqueous phase was extracted with dichloromethane
  10. dry with materialThe combined organic phases were dried over sodium sulfate
  11. filtrationfiltered
  12. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-e984f836f37d4b35bcd967aeb7d1756a
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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