Phosphorus oxychloride → octanedioic acid [4-(3-Nitro-phenyl)-thiazol-2-yl]-amide methyl ester

HRID 243620

Reaction equation

HRID 243620 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[N:11]=[C:12]([NH2:15])[S:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH3:16][O:17][C:18](=[O:28])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](O)=[O:26].O=P(Cl)(Cl)Cl>N1C=CC=CC=1.CCOC(C)=O>[CH3:16][O:17][C:18](=[O:28])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([NH:15][C:12]1[S:13][CH:14]=[C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[N:11]=1)=[O:26]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 5541918-Methoxy-8-oxooctanoic acidHCID 6135042-Amino-4-(3-nitrophenyl)thiazole

Product 1

HCID 44550802octanedioic acid [4-(3-Nitro-phenyl)-thiazol-2-yl]-amide methyl esterYield 61.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirring solution of 4-(3-nitrophenyl)-thiazol-2-ylamine (11) (2.21 g, 10 mmol) and suberic acid monomethyl ester (13) (1.88 g, 10 mmol) in dry pyridine (20 ml) was cooled to −15° C. and POCl3 (1.2 ml, 13 mmol) was added dropwise over 30 minutes. After stirring for another 1 hour at same temperature, the reaction mixture was diluted with EtOAc and washed thoroughly with 1N HCl solution and brine. The organic phase was dried over Na2SO4. The solvent was removed by rotary evaporation. The crude solid was washed with EtOAc to give compound 14 (2.40 g, 61.5%). 1H NMR (400 MHz, DMSO-d6) δ12.3 (1H, s), 8.74 (1H, d, J=1.4 Hz), 8.35 (1H, d, J=7.1 Hz), 8.18 (1H, d, J=7.8 Hz), 7.93 (1H, s), 7.74 (1H, t, J=7.9 Hz), 3.58 (3H, s), 2.46 (2H, t, J=7.5 Hz), 2.30 (2H, t, J=7.3 Hz), 1.61 (2H, t, J=6.5 Hz), 1.53 (2H, t, J=6.8 Hz), 1.30 (4H, brs). 13C NMR (100 MHz, DMSO-d6) δ172.1, 158.8, 148.7, 146.7, 136.2, 132.1, 130.8, 122.7, 120.5, 110.8, 51.6, 35.2, 33.6, 28.6, 28.5, 24.8, 24.6.

Workup

  1. washwashed thoroughly with 1N HCl solution and brine
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customThe solvent was removed by rotary evaporation
  4. washThe crude solid was washed with EtOAc

Sources & evidence

ORD record
ord-1af3149478724c9ebc1f347585fe949b
Source dataset
uspto-grants-2014_02
Patent number
US08653278B2

Linked notes

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