Sodium hydride → 7-Methoxy-1-[4-((R)-1-phenyl-ethoxy)-phthalazin-1-yl]-naphthalen-2-ol

HRID 1711980

Reaction equation

HRID 1711980 reaction equation
[H-].[Na+].[C:3]1([C@H:9]([OH:11])[CH3:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=3)[CH:26]=[CH:25][C:24]=2[OH:35])=[N:15][N:14]=1>O1CCCC1>[CH3:34][O:33][C:30]1[CH:31]=[C:32]2[C:27]([CH:26]=[CH:25][C:24]([OH:35])=[C:23]2[C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:13]([O:11][C@@H:9]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH3:10])=[N:14][N:15]=2)=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6375161-Phenylethanol, (R)-HCID 1363434531-(4-Chlorophthalazin-1-yl)-7-methoxynaphthalen-2-ol

Product 1

HCID 1363525037-Methoxy-1-[4-((R)-1-phenyl-ethoxy)-phthalazin-1-yl]-naphthalen-2-olYield 86.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (0.80 g, 33 mmol) in tetrahydrofuran (80 ml) was added a solution of (R)-phenylethanol (2.0 g, 17 mmol) in tetrahydrofuran (3 ml) cautiously over 10 min at 23° C. The mixture was stirred for 15 min, then 1-(4-chlorophthalazin-1-yl)-7-methoxy-naphthalen-2-ol (5.1 g, 15 mmol) was added portionwise. The resulting red suspension was stirred for 20 hrs at 23° C., then the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and poured into brine. The organic layer was separated and the aqueous layer was extracted two times with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (hexane/EtOAc 4:1 to 1:1) to give 5.5 g (13 mmol) of the title compound as a 1:1 mixture of diastereomers, as a white foam.

Workup

  1. stirringThe resulting red suspension was stirred for 20 hrs at 23° C.
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane
  4. additionpoured into brine
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted two times with dichloromethane
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (hexane/EtOAc 4:1 to 1:1)

Sources & evidence

ORD record
ord-984b8e45f7044bec9fc262c677bde064
Source dataset
uspto-grants-2010_09
Patent number
US07790882B2

Linked notes

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