Benzylamine → 4-(5-Benzylamino-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-benzamide

HRID 422254Notes

Reaction equation

HRID 422254 reaction equation
O=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][CH:14]=3)[CH:5]=[CH:4][C:3]1=2.[CH2:22]([NH2:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH-].[Na+]>CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.Cl[Ti](Cl)(Cl)Cl.C1COCC1>[CH2:22]([NH:29][CH:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][CH:14]=3)[CH:5]=[CH:4][C:3]1=2)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 3

HCID 7504BenzylamineHCID 14798Sodium HydroxideHCID 597506504-(5-Oxo-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-benzamide2×

Product 1

HCID 597506744-(5-Benzylamino-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-benzamideYield 12%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 178460666HCID 178460666, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Combine 4-(5-Oxo-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-benzamide (Intermediate 26, 120.0 mg, 0.43 mmol), Benzylamine (70 uL, 0.64 mmol), THF (3 mL), and Ti(OiPr)4 (0.2 mL, 0.68 mmol) at 0° C. Stir the reaction for 12 hours allowing it to come to room temperature and then add TiCl4 (0.7 mL, 0.68 mmol) at 0° C. After reaction stirs for 3 hours, add BH3SMe2 at room temperature. After the reaction stirs for 72 hours, add 1N NaOH aq (6 mL) at room temperature. Upon addition, a precipitate forms. Allow the reaction to stir for an additions 12 hours, centrifuge, and decant off aqueous and organic layers. Separate the organic layer and concentrate. Add the organic mixture to a 2 g SCX column, wash with MeOH, and elute with 1N NH3 MeOH. Purify using reverse phase chromatography (5% to 95% 0.001% TFA buffer in acetonitrile/water) to afford 19.4 mg, 0.05 mmol (12% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 1.7-1.8 (2H, m), 1.9-2.1 (3H, m), 2.6-2.9 (2H, m), 3.8-4.0 (3H, m), 6.7-6.9 (2H, m), 6.9-7.0 (2H, m), 7.2-7.5 (6H, m), 7.7-7.9 (2H, m); MS m/z 284 (M of SM+3).

Workup

  1. customat 0° C
  2. customthe reaction for 12 hours
  3. customto come to room temperature
  4. customat 0° C
  5. customAfter reaction stirs for 3 hours
  6. additionadd BH3SMe2 at room temperature
  7. additionUpon addition
  8. customAllow the reaction
  9. stirringto stir for an additions 12 hours, centrifuge
  10. customdecant off aqueous
  11. customSeparate the organic layer
  12. concentrationconcentrate
  13. additionAdd the organic mixture to a 2 g SCX column
  14. washwash with MeOH
  15. washelute with 1N NH3 MeOH
  16. customPurify

Sources & evidence

ORD record
ord-4c4594e06d1645269f3f676a11d832ce
Source dataset
uspto-grants-2012_01
Patent number
US08101638B2

Reaction notes

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