p-Fluorophenethylamine → N-[2-(4-Fluorophenyl)ethyl]-3-[2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)-2-methylpropyl]benzamide

HRID 1866494Notes

Reaction equation

HRID 1866494 reaction equation
[Si]([O:8][C@H:9]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH2:32][OH:33])[CH:26]=1)[CH2:10][NH:11][C:12]([CH3:24])([CH3:23])[CH2:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18])(C(C)(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:58][C:59]1[CH:67]=[CH:66][C:62]([CH2:63][CH2:64][NH2:65])=[CH:61][CH:60]=1.[F-].[NH4+]>CN(C)C(=O)C.CO.O>[F:58][C:59]1[CH:67]=[CH:66][C:62]([CH2:63][CH2:64][NH:65][C:17](=[O:18])[C:16]2[CH:20]=[CH:21][CH:22]=[C:14]([CH2:13][C:12]([NH:11][CH2:10][C@H:9]([OH:8])[C:25]3[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH2:32][OH:33])[CH:26]=3)([CH3:23])[CH3:24])[CH:15]=2)=[CH:61][CH:60]=1

Participants

8

Reactant 4

HCID 4653p-FluorophenethylamineHCID 25516Ammonium fluorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579783093-{2-[(2R)-2-(tert-butyldimethyl silanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}benzoic acid

Product 1

HCID 11363643N-[2-(4-Fluorophenyl)ethyl]-3-[2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)-2-methylpropyl]benzamideYield 50%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent3×

Procedure

Solutions of 3-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxy methylphenyl)ethylamino]-2-methylpropyl}benzoic acid (preparation 37) (90 mg, 0.19 mmol) in N,N-dimethylacetamide (1 mL) and O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (61 mg, 0.16 mmol) in N,N-dimethylacetamide (0.5 mL) were added to a solution of 4-fluorophenethylamine (33 mg, 0.19 mmol) in N,N-dimethylacetamide (0.5 mL). The resulting mixture was stirred for 72 hours at room temperature. The solvent was removed in vacuo and the residue was partitioned between dichloromethane (4 mL) and saturated sodium hydrogen carbonate solution (1 mL). The mixture was then filtered through a phase separation tube and the organic solution was concentrated in vacuo. Ammonium fluoride (70 mg, 1.9 mmol) was added to a suspension of the residue in methanol (2 mL) and water (1 mL) and the mixture was stirred at room temperature for 72 hours. The reaction mixture was then concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 100:0:0 to 91:9:1, followed by trituration with diethyl ether, to afford the title compound in 50% yield, 45 mg. 1H NMR (400 MHz, CD3OD) δ: 7.63 (2H, m), 7.40-7.30 (3H, m), 7.23 (2H, m), 7.14 (1H, m), 7.00 (2H, m), 6.75 (1H, d), 4.65 (3H, m), 3.58 (2H, m), 2.98-2.64 (6H, m), 1.11 (3H, s), 1.05 (3H, s) ppm; LRMS APCI m/z 481 [M+H]+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between dichloromethane (4 mL) and saturated sodium hydrogen carbonate solution (1 mL)
  3. filtrationThe mixture was then filtered through a phase separation tube
  4. concentrationthe organic solution was concentrated in vacuo
  5. concentrationThe reaction mixture was then concentrated in vacuo
  6. customthe residue was purified by column chromatography on silica gel
  7. washeluting with dichloromethane

Sources & evidence

ORD record
ord-331402bf34984761926577e8aaad4533
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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