Diisopropylethylamine → HCID 22643460, compound

HRID 354152

Reaction equation

HRID 354152 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 22643460HCID 22643460, compoundYield 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-f2bd5aa8a41a4770aa48fc50599d2866
Source dataset
uspto-grants-2004_06
Patent number
US06756393B2

Linked notes

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