Potassium Carbonate → [(3-{[4-(Methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]dec-7-ylmethyl]amino)-4-nitrobenzonitrile

HRID 715516

Reaction equation

HRID 715516 reaction equation
[NH2:1][CH2:2][C:3]1([CH2:23][O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:22][CH2:21][CH2:20][C:5]2([O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[CH2:6]2)[CH2:4]1.C(=O)([O-])[O-].[K+].[K+].F[C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[N+:47]([O-:49])=[O:48])[C:42]#[N:43]>C(#N)C>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:7]2[CH2:6][C:5]3([CH2:20][CH2:21][CH2:22][C:3]([CH2:2][NH:1][C:44]4[CH:45]=[C:46]([N+:47]([O-:49])=[O:48])[CH:39]=[CH:40][C:41]=4[C:42]#[N:43])([CH2:23][O:24][CH2:25][C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:4]3)[O:9][C:8]2=[O:10])=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27833993-Fluoro-4-nitrobenzonitrileHCID 711161567-(Aminomethyl)-7-((benzyloxy)methyl)-3-(4-methoxybenzyl)-1-oxa-3-azaspiro[4.5]decan-2-one

Product 1

HCID 86717583[(3-{[4-(Methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]dec-7-ylmethyl]amino)-4-nitrobenzonitrileYield 87.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a light yellow solution of 7-(aminomethyl)-7-((benzyloxy)methyl)-3-(4-methoxybenzyl)-1-oxa-3-azaspiro[4.5]decan-2-one (4.27 g, 10.1 mmol) in acetonitrile (67.1 mL) was added potassium carbonate (2.78 g, 20.1 mmol) and 3-fluoro-4-nitrobenzonitrile (2.51 g, 15.1 mmol) and the reaction was stirred at RT. After stirring 15 h, the reaction was filtered through a frit. The collected inorganics were washed with DCM/EtOAc. The filtrate was concentrated onto florisil and purified on a 80 g silica gel column (20-55% EtOAc/hexanes, 30 min gradient; 55% EtOAc/hexanes, 5 min.; 60 mL/min elution; 254 nm detection) to provide 3-{[(3-{[4-(methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]dec-7-ylmethyl]amino)-4-nitrobenzonitrile (5.02 g, 83% yield) as a reddish-orange oil. MS (m/z) 571.0 (M+H+).

Workup

  1. stirringAfter stirring 15 h
  2. filtrationthe reaction was filtered through a frit
  3. washThe collected inorganics were washed with DCM/EtOAc
  4. concentrationThe filtrate was concentrated onto florisil
  5. custompurified on a 80 g silica gel column (20-55% EtOAc/hexanes, 30 min gradient; 55% EtOAc/hexanes, 5 min.; 60 mL/min elution; 254 nm detection)

Sources & evidence

ORD record
ord-b5bc105ffcaa43a6a7eb6fc5e6b750df
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Linked notes

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