Water → 6-Fluoro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 1727403Notes

Reaction equation

HRID 1727403 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[OH:11])[C:7](=[O:12])[CH2:6][CH2:5]2.[N-:13]=[N+]=[N-].[Na+].O>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[OH:11])[C:7](=[O:12])[NH:13][CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 962WaterHCID 33557Sodium AzideHCID 448291085-Fluoro-6-hydroxy-2,3-dihydro-1H-inden-1-one

Product 1

HCID 575676666-Fluoro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of (90) (10.5 g, 63.3 mmol) in chloroform (600 ml) was added NaN3 (12.3 g, 190 mmol), followed by dropwise addition of methanasulfonic acid (33 ml, 506 mmol). Resulting mixture was stirred for 3 hr. The reaction mixture was poured into cold water and extracted with chloroform (3×). Organic extracts were combined and washed with H2O and sat. NaCl, then dried over Na2SO4. Concentration in vacuo gave a mixture of required product and reversed lactam. Purification of crude product on silica eluting with 30-60% EtOAc/Hex offered WAY-263746 as a off-white solid (5.3 g, 46%). 1H NMR/CD3OD, δ, 7.48 (d, 1H), 7.00 (d, 1H), 3.43-3.49 (t, 2H), 2.83-2.89 (t, 2H). MS (ES) m/z 180.0.

Workup

  1. customResulting mixture
  2. extractionextracted with chloroform (3×)
  3. washwashed with H2O and sat. NaCl
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration in vacuo
  6. customgave

Sources & evidence

ORD record
ord-e9e88c748b9e4b5eae3803dfffc987b5
Source dataset
uspto-grants-2009_02
Patent number
US07495111B2

Reaction notes

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