Hydrochloric Acid → [6-Hydroxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513926Notes

Reaction equation

HRID 1513926 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:17][CH:16]=1)=[O:14])=[C:8]([C:30]1[C:35]([F:36])=[CH:34][C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH:7]=[CH:6]2.Cl.C(OCC)C.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl.CO>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]3)=[CH:17][CH:16]=1)=[O:14])=[C:8]([C:30]1[C:35]([F:36])=[CH:34][C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH:7]=[CH:6]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 57552534[6-Methoxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Product 1

HCID 67004176[6-Hydroxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 87%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Alternatively, dissolve [6-methoxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (1.90 g, 3.67 mmol) in dichloromethane (10 ml). Add 2 M HCl in diethyl ether (4.0 mL, 80 mmol). Concentrate the slurry and dry in vacuo. Dilute the residue in dichloromethane (30 ml) and blanket with nitrogen. Cool the solution to 0° C. with an external ice bath. Add boron tribromide (1 mL, 11 mmol). After 60 minutes, pour the reaction mixture into a mixture of ice (20 g), methanol (10 mL) and saturated sodium bicarbonate solution (20 mL). Extract with dichloromethane (100 mL). Separate the layers, wash the organic layer with brine (20 mL), dry with magnesium sulfate, filter, and concentrate in vacuo. Purify the residue over silica gel, eluting the material with a step gradient of methanol/dichloromethane (0 to 10%), to give 1.6 g (87%) of the title compound: mass spectrum (ion spray) m/z=506.2 (M+H).

Workup

  1. concentrationConcentrate the slurry
  2. customdry in vacuo
  3. additionDilute the residue in dichloromethane (30 ml)
  4. additionpour the reaction mixture
  5. extractionExtract with dichloromethane (100 mL)
  6. customSeparate the layers
  7. washwash the organic layer with brine (20 mL)
  8. dry with materialdry with magnesium sulfate
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customPurify the residue over silica gel
  12. washeluting the material with a step gradient of methanol/dichloromethane (0 to 10%)

Sources & evidence

ORD record
ord-82f4eacc500944e3be5f6007ab38bfb6
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…