Pyridine → HCID 86638053, compound

HRID 1668569Notes

Reaction equation

HRID 1668569 reaction equation
[OH:1][C:2]1[C:3]([C:19](=O)[CH3:20])=[CH:4][C:5]2[CH2:11][CH2:10][N:9]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:8][CH2:7][C:6]=2[CH:18]=1.[N:22]1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>O>[CH3:20][C:19]1[C:3]2[C:2](=[CH:18][C:6]3[CH2:7][CH2:8][N:9]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:10][CH2:11][C:5]=3[CH:4]=2)[O:1][N:22]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 59150507HCID 59150507, compound

Product 1

HCID 86638053HCID 86638053, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 1-[8-hydroxy-3-(trifluoroacetyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]ethanone (7.4 mmol) in pyridine (15 ml) hydroxylamine hydrochloride (8.9 mmol) was added at room temperature and the reaction mixture was stirred for 4 h. Solvent was removed under reduced pressure, the residue was partitioned between 10% aqueous Na2CO3 and EtOAc. The organic layer was collected and the aqueous phase extracted twice with EtOAc. The combined organic layers were concentrated and the resulting material was dissolved in THF (5 ml) and Ph3P (15 mmol) was added. The reaction mixture was stirred at 50° C. for 10 min while DEAD (15 mmol, 40% in toluene) was slowly added. The reaction mixture was stirred at 50° C. for 15 min then cooled to room temperature and water (0.4 ml) was added. Solvent was removed under reduced pressure and the residue was submitted to column chromatography to provide 3-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-isoxazolo[4,5-h][3]benzazepine (NMR 1H, CDCl3): δ 7.4-7.3 (m, 2H), 3.85-3.65 (m, 4H), 3.15-3.05 (m, 4H), 2.55 (s, 3H). MS (m/z): 299 [MH]+). Treatment with K2CO3 (4 eq) in MeOH:H2O (1:1) gave the title compound (1.3 mmol) as pale yellow oil, which was used without further characterisation.

Workup

  1. customSolvent was removed under reduced pressure
  2. customthe residue was partitioned between 10% aqueous Na2CO3 and EtOAc
  3. customThe organic layer was collected
  4. extractionthe aqueous phase extracted twice with EtOAc
  5. concentrationThe combined organic layers were concentrated
  6. dissolutionthe resulting material was dissolved in THF (5 ml)
  7. additionwas slowly added
  8. stirringThe reaction mixture was stirred at 50° C. for 15 min
  9. customSolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8daa393b398542efaec7be4463efdafa
Source dataset
uspto-grants-2011_08
Patent number
US07989444B2

Reaction notes

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