Diisopropylethylamine → N-((4-methylphenyl)methyl)-N-(1-methylpiperidin-4-yl)-2-(3-hydroxy-4-methoxyphenyl)acetamide

HRID 2414904Notes

Reaction equation

HRID 2414904 reaction equation
[CH3:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH:17][C:18]1[CH:19]=[C:20]([CH2:26][C:27](O)=[O:28])[CH:21]=[CH:22][C:23]=1[O:24][CH3:25].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>CN(C=O)C.O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[C:27](=[O:28])[CH2:26][C:20]2[CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:18]([OH:17])[CH:19]=2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1605623-Hydroxy-4-methoxybenzeneacetic acidHCID 2733179PyBroPHCID 11993862HCID 11993862, compound

Product 1

HCID 22643460N-((4-methylphenyl)methyl)-N-(1-methylpiperidin-4-yl)-2-(3-hydroxy-4-methoxyphenyl)acetamideYield 280%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

N-((4-methylphenyl)methyl)-4-amino-1-methylpiperidine (50ELH25) (105 mg, 0.48 mmol) and 3-hydroxy-4-methoxyphenylacetic acid (88 mg, 0.48 mmol) were dissolved in DMF (10 ml). Diisopropylethylamine (DIEA, 250 μL, 1.44 mmol) was added followed by bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP, 336 mg, 0.72 mmol), and the mixture was stirred at r.t for 1 h. Water (50 mL) was added, and the reaction mixture was extracted with EtOAc (2×50 mL). Drying by Na2SO4 and concentration yielded 514 mg crude material, which was purified by flash chromatography (0-30% MeOH in CH2Cl2). This gave 105 mg (57%) of the title compound as a white solid. Rf=0.20 (10% MeOH in CH2Cl2). HPLC-MS (method A) showed MH+=383. UV/MS(%)=100/92. 1H-NMR (400 MHz, CD3OD, Rotamers 52:48): δ 7.18-6.58 (m, 7H), 4.53 (s, 2H), 4.31 and 3.97 (2m, 1H), 3.82 and 3.81 (2s, 3H), 3.80 and 3.55 (2s, 2H), 3.04 and 2.85 (2m, 2H), 2.41 and 2.32 (2s, 3H), 2.35 and 2.12 (2m, 2H), 2.29 and 2.27 (2s, 3H), 1.83 and 1.74 (2m, 2H), 1.72 and 1.33 (2m, 2H)

Workup

  1. extractionthe reaction mixture was extracted with EtOAc (2×50 mL)
  2. dry with materialDrying by Na2SO4 and concentration

Sources & evidence

ORD record
ord-a77a0754a41a4c9e9810a45f941a4749
Source dataset
uspto-grants-2004_11
Patent number
US06815458B2

Reaction notes

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