4-Fluorophenol → HCID 86644307, compound

HRID 876365Notes

Reaction equation

HRID 876365 reaction equation
[CH3:1][N:2]1[CH2:8][CH2:7][CH:6](O)[C:5]2[CH:10]=[CH:11][C:12]([C:14]3[N:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:13][C:4]=2[CH2:3]1.FC1C=CC(O)=CC=1>C1COCC1.ClCCl>[CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][C:5]2[CH:10]=[CH:11][C:12]([C:14]3[N:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:13][C:4]=2[CH2:3]1

Participants

5

Reactant 2

HCID 97324-FluorophenolHCID 68502906HCID 68502906, compound

Product 1

HCID 86644307HCID 86644307, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the 2-methyl-8-(pyridazin-3-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-ol (170 mg, 0.67) from Step H above in THF (5 mL) was added 4-fluorophenol (98 mg, 0.87 mmol), tributylphosophine (176 mg, 0.52 mmol) and 1,1′-(azodicarboyl)dipiperidine (220 mg, 0.87 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 hours. The mixture was diluted with dichloromethane and washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography (98:2 to 95:5 ethyl acetate/methanol), followed by preparative HPLC to give 544-fluorophenoxy)-2-methyl-8-(pyridazin-3-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine (120 mg, 51%) as a gum-like solid. This compound was resolved using Chiralcel OJ column (eluente:80 Hep:20 EtOH:0.1 DEA) to give (+)-enantiomer (36 mg)) and (−)-enantiomer (37 mg).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography (98:2 to 95:5 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-d1791e390ccc44d8aa929fcc2a359443
Source dataset
uspto-grants-2015_03
Patent number
US08987252B2

Reaction notes

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