Triphenylphosphine → HCID 24878307, compound

HRID 902297Notes

Reaction equation

HRID 902297 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[O:16][C@@H:15]([CH2:18][N:19]=[N+]=[N-])[CH2:14][CH2:13]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[O:16][C@@H:15]([CH2:18][NH2:19])[CH2:14][CH2:13]2

Participants

5

Reactant 2

HCID 11776TriphenylphosphineHCID 86609101HCID 86609101, compound

Product 1

HCID 24878307HCID 24878307, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {[(2R)-8-(2-chlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}azide (0.14 g, 0.47 mmol) in tetrahydrofuran (7.8 mL) and water (0.8 mL) was added polymer-bound triphenylphosphine (˜3 mmol/g, 0.36 g, 1.08 mmol) and the mixture gently shaken for 3 days. The brown suspension was then filtered through celite, the filter cake washed with diethyl ether (10 mL) and the combined filtrates dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. The crude product was purified by reverse phase HPLC using a solvent gradient of 5 to 95% acetonitrile in water containing 0.1% trifluoroacetic acid. The fractions containing product were concentrated under reduced pressure to remove acetonitrile and the aqueous phase basified by the addition of sodium carbonate and then extracted with ethyl acetate (100 mL). The separated organic phase was dried over magnesium sulfate and concentrated under reduced pressure to afford {[(2R)-8-(2-chlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}amine as a yellow syrup. The product was dissolved in diethyl ether (1 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.25 mL, 0.25 mmol) was added followed by 2-propanol (2 drops). The resulting white precipitate was filtered and the solid product triturated with diethyl ether (3×3 mL) to afford 36 mg (25%) of {[(2R)-8-(2-chlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}amine hydrochloride as a white solid.

Workup

  1. filtrationThe brown suspension was then filtered through celite
  2. washthe filter cake washed with diethyl ether (10 mL)
  3. dry with materialthe combined filtrates dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a yellow oil
  7. customThe crude product was purified by reverse phase HPLC
  8. additionThe fractions containing product
  9. concentrationwere concentrated under reduced pressure
  10. customto remove acetonitrile
  11. additionthe aqueous phase basified by the addition of sodium carbonate
  12. extractionextracted with ethyl acetate (100 mL)
  13. dry with materialThe separated organic phase was dried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4e4860e5abb24f12ac58b61492bf7fc3
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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