Benzophenone imine → HCID 86607828, compound

HRID 1821996Notes

Reaction equation

HRID 1821996 reaction equation
Br[C:2]1[C:3]([F:16])=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]1.[C:17](=[NH:30])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:17](=[N:30][C:2]1[CH:15]=[CH:14][CH:13]=[C:4]([O:5][CH:6]2[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[C:3]=1[F:16])([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 57893694HCID 57893694, compound

Product 1

HCID 86607828HCID 86607828, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Heat a mixture of 4-(3-bromo-2-fluoro-phenoxy)-1-methyl-piperidine (preparation 18 or 19, 1.60 g), benzhydrylideneamine (1.21 g), tris(dibenzylidineacetone)-dipalladium(0) (0.11 g), racemic-2,2′-bis(diphenylphosphino)-1,1′binaphthyl (0.138 g) and sodium t-butoxide (0.75 g) in toluene (100 mL) and reflux. After 3 hr., cool to room temperature, load on a SCX column (10 g), wash with methanol, elute the product with 2 M NH3 in methanol. Evaporate the NH3-methanol solution and purify on a 35 g silica gel column eluting with dichloromethane-2M NH3 in methanol, gradient to give benzhydrylidene-[2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-amine. Dissolve the amine in THF and add 1N HCl. After 10 min., basify with NH4OH and partition between ethyl acetate and saturated aqueous NaCl, dry over sodium sulfate, evaporate and purify on a 35 g silica gel column eluting with: dichloromethane-2M NH3 in methanol, gradient) to give the title compound (1.19 g): mass spectrum (electric spray) m/z=225 (M+1); 1H NMR (CDCl3): 6.78 (m, 1H), 6.38 (m, 2H), 4.25 (m, 1H), 3.73 (br s, 2H), 2.69 (m, 2H), 2.27 (s, 3H), 2.26 (m, 2H), 1.97 (m, 2H), 1.87 (m, 2H).

Workup

  1. temperatureHeat
  2. temperaturereflux
  3. washload on a SCX column (10 g), wash with methanol
  4. washelute the product with 2 M NH3 in methanol
  5. customEvaporate the NH3-methanol solution
  6. custompurify on a 35 g silica gel column
  7. washeluting with dichloromethane-2M NH3 in methanol, gradient

Sources & evidence

ORD record
ord-dc17d26697054d1a840390fe70248991
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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