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

HRID 1513971Notes

Reaction equation

HRID 1513971 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29]C)=[CH:26][CH:27]=4)[CH:22]=[CH:21][C:20]=3[C:31]3[C:36]([F:37])=[CH:35][C:34]([F:38])=[CH:33][C:32]=3[F:39])=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl.CO>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:28]4[C:23](=[CH:24][C:25]([OH:29])=[CH:26][CH:27]=4)[CH:22]=[CH:21][C:20]=3[C:31]3[C:36]([F:37])=[CH:35][C:34]([F:38])=[CH:33][C:32]=3[F:39])=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 57552563[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[6-methoxy-2-(2,4,6-trifluoro phenyl)-naphthalen-1-yl]-methanone

Product 1

HCID 67004267[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[6-hydroxy-2-(2,4,6-trifluoro-phenyl)naphthalen-1-yl]-methanoneYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve [4-(2-azepan-1-yl-ethoxy)-phenyl]-[6-methoxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-methanone (634 mg, 1.2 mmol) in dichloromethane (10 mL). Cool to 0° C., add HCl (2M in ether, 1.2 mL, 2.4 mmol) and stir at room temperature for 15 minutes. Concentrate in vacuo. Redissolve the salt in dichloromethane (10 mL) and cool to 0° C. Add boron tribromide (949 mg, 3.6 mmol) dropwise and bring to room temperature. Stir reaction for 1.5 hours and pour reaction mixture onto ice, saturated sodium bicarbonate (20 mL) and methanol (20 mL). Extract with dichloromethane, combine extracts and wash with water and saturated sodium bicarbonate. Dry with sodium sulfate, filter, and concentrate in vacuo. Purify by silica gel chromatography using a 1-3% gradient of methanol in dichloromethane to yield 350 mg (57%) of the title compound: mass spectrum (ion spray) m/z=520 (M+H).

Workup

  1. concentrationConcentrate in vacuo
  2. dissolutionRedissolve the salt in dichloromethane (10 mL)
  3. temperaturecool to 0° C
  4. custombring to room temperature
  5. stirringStir
  6. customreaction for 1.5 hours
  7. additionpour
  8. extractionExtract with dichloromethane
  9. washwash with water and saturated sodium bicarbonate
  10. dry with materialDry with sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. customPurify by silica gel chromatography

Sources & evidence

ORD record
ord-b5c4da962ce24488918024477141b354
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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